bluuebunny/crossref_metadata_2025 huggingface dataset:
More illness and less disease? A 20-year perspective on chronic disease and medication
Authors: Hagstrom Bertil , Mattsson Bengt , Wimo Anders , Gunnarsson Ronny K.
Published: June 2006

Background: The implication of medication is that a drug is given against an illness. Over the last few decades an expanding number of drugs have appeared that focus on reducing risk factors and lifestyle conditions. Aims: To investigate the apprehension in respect of chronic disease among the working population in a Swedish community in 2000 compared with 1980. Methods: In 1980 and 2000 an analogous questionnaire assessing chronic diseases and medication was mailed to 250 randomly selected persons from a local population between 25 and 70 years of age. Results: Some 80% of the persons (n=201) replied in 1980 and 78% (n=195) in 2000. Individuals declaring a chronic disease increased from 23% (46/201) in 1980 to 39.5% in 2000 (p=0.0005). Corresponding figures for men were 20.6% (20/97) in 1980 and 40.8% (40/98) in 2000 (p=0,004) and for women 25.0% (26/104) in 1980 and 38.1% (37/97) in 2000 (p=0.064). Persons who regularly see a doctor increased from 13% to 26% (p=0.002) and the use of drugs for chronic diseases increased from 19% to 33% (p=0.002). In 2000 an average of 2.3 drugs per person were used among those with a chronic disease, an increase of 53% since 1980. Conclusion: Stated chronic diseases and use of drugs for such diseases increased greatly between1980 and 2000. Prescribing drugs for a ``risk'' with no apparent illness may be confused with the remedy for an illness.
Risk-factor profile for the incidence of subarachnoid and intracerebral haemorrhage, cerebral infarction, and unspecified stroke during 21 years' follow-up in men
Authors: Håheim Lise Lund , Holme Ingar , Hjermann Ingvar , Tonstad Serena
Published: June 2006

Aims: To study the risk-factor profile for the incidence of non-fatal and fatal stroke among middle-aged men according to the stroke subtypes subarachnoid or intracerebral haemorrhage, cerebral infarction, and unspecified stroke. Methods: The study design is a prospective cohort study. A total of 16,209 men aged 40—49 years resident in Oslo were screened for cardiovascular disease risk factors in 1972—73. Of these, 14,403 men had no cardiovascular symptoms or diseases or diabetes. The incidence of stroke after 21 years of follow-up of all men was extracted from hospital records and linkage to Statistics Norway. Results: A total of 429 non-fatal and 107 fatal stroke events were registered. Case fatality within 28 days (number and percentage of cases) was 51% (41, 7.7%) for subarachnoid haemorrhage, 39% (67, 12.6%) for cerebral haemorrhage, 10% (246, 46.3%) for cerebral infarct, and 19% (177, 33.4%) for unspecified stroke. Risk of stroke (not subarachnoid haemorrhage) increased with the presence of symptoms or a history of cardiovascular disease or diabetes. In multivariate analysis of men without CVD or diabetes, high blood pressure was a risk factor for all subtypes of stroke; furthermore, daily smoking was a risk factor for all subtypes except subarachnoid haemorrhage. Serum cholesterol and glucose concentrations and height (inverse association) were independently associated with cerebral infarction. Smoking was a significantly stronger predictor of fatal than non-fatal events. Conclusions: The risk-factor profile differed according to the underlying subtype of stroke. Cerebral infarction clearly shared with myocardial infarction the classical risk factors, including non-fasting glucose concentration.
Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase–mediated apoptosis of HeLa cells
Authors: Yim Hyungshin , Hwang In Sun , Choi Joon-Seok , Chun Kwang-Hoon , Jin Ying Hua , Ham Young-Mi , Lee Kwang Youl , Lee Seung Ki
Published: June 2006

We show that caspase-3 cleaves Cdc6 at D290/S and D442/G sites, producing p32-tCdc6 (truncated Cdc6) and p49-tCdc6, respectively, during etoposide- or tumor necrosis factor (TNF)-α–induced apoptosis. The expression of these tCdc6 proteins, p32- and p49-tCdc6, promotes etoposide-induced apoptosis. The expression of tCdc6 perturbs the loading of Mcm2 but not Orc2 onto chromatin and activates ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) kinase activities with kinetics similar to that of the phosphorylation of Chk1/2. The activation kinetics are consistent with elevated cellular levels of p53 and mitochondrial levels of Bax. The tCdc6-induced effects are all suppressed to control levels by expressing a Cdc6 mutant that cannot be cleaved by caspase-3 (Cdc6-UM). Cdc6-UM expression attenuates the TNF-α–induced activation of ATM and caspase-3 activities. When ATM or ATR is down-expressed by using the small interfering RNA technique, the TNF-α– or tCdc6-induced activation of caspase-3 activities is suppressed in the cells. These results suggest that tCdc6 proteins act as dominant-negative inhibitors of replication initiation and that they disrupt chromatin structure and/or induce DNA damage, leading to the activation of ATM/ATR kinase activation and p53–Bax-mediated apoptosis.
Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery
Authors: Togashi Hideru , Miyoshi Jun , Honda Tomoyuki , Sakisaka Toshiaki , Takai Yoshimi , Takeichi Masatoshi
Published: June 2006

Neurites recognize their specific partners during the formation of interneuronal connections. In hippocampal pyramidal neurons, axons attach to dendrites for their synaptogenesis, but the dendrites do not form stable contacts with each other, suggesting the presence of a mechanism to allow their selective associations. Nectin-1 (N1), an immunoglobulin domain adhesive protein, is preferentially localized in axons, and its heterophilic partner, N3, is present in both axons and dendrites; we tested their potential roles in interneurite recognition. The overexpression of N1, causing its mislocalization to dendrites, induced atypical dendrodendritic as well as excessive axodendritic associations. On the contrary, the genetic deletion of N1 loosened the contacts between axons and dendritic spines. Those actions of nectins required cadherin–catenin activities, but the overexpression of cadherin itself could not accelerate neurite attachment. These results suggest that the axon-biased localization of N1 and its trans-interaction with N3 in cooperation with the cadherin machinery is critical for the ordered association of axons and dendrites.
Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction
Authors: Witsch Esther J. , Cao Hong , Fukuyama Hidehiro , Weigert Martin
Published: June 2006

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4+ T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and β-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with “editor” L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress κ and λ L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal
Authors: You Han , Pellegrini Marc , Tsuchihara Katsuya , Yamamoto Kazuo , Hacker Georg , Erlacher Miriam , Villunger Andreas , Mak Tak W.
Published: June 2006

Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, Puma is induced in a p53-dependent manner. However, the transcription factor driving Puma up-regulation in response to p53-independent apoptotic stimuli has yet to be identified. Here, we show that FOXO3a up-regulates Puma expression in response to cytokine or growth factor deprivation. Importantly, dysregulated Akt signaling in lymphoid cells attenuated Puma induction upon cytokine withdrawal. Our results suggest that Puma, together with another BH3 only member, Bim, function as FOXO3a downstream targets to mediate a stress response when PI3K/Akt signaling is down-regulated.
Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-κB in B cell clonal anergy
Authors: Bléry Mathieu , Tze Lina , Miosge Lisa A. , Jun Jesse E. , Goodnow Christopher C.
Published: June 2006

Divergent hypotheses exist to explain how signaling by the B cell receptor (BCR) is initiated after antigen binding and how it is qualitatively altered in anergic B cells to selectively uncouple from nuclear factor κB and c-Jun N-terminal kinase pathways while continuing to activate extracellular signal–regulated kinase and calcium–nuclear factor of activated T cell pathways. Here we find that BCRs on anergic cells are endocytosed at a very enhanced rate upon binding antigen, resulting in a large steady-state pool of intracellularly sequestered receptors that appear to be continuously cycling between surface and intracellular compartments. This endocytic mechanism is exquisitely sensitive to the lowering of plasma membrane cholesterol by methyl-β-cyclodextrin, and, when blocked in this way, the sequestered BCRs return to the cell surface and RelA nuclear accumulation is stimulated. In contrast, when plasma membrane cholesterol is lowered and GM1 sphingolipid markers of membrane rafts are depleted in naive B cells, this does not diminish BCR signaling to calcium or RelA. These results provide a possible explanation for the signaling changes in clonal anergy and indicate that a chief function of membrane cholesterol in B cells is not to initiate BCR signaling, but instead to terminate a subset of signals by rapid receptor internalization.
Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose–response using different monomers
Authors: Senden R J , De Jean P , McAuley K B , Schreiner L J
Published: June 2006

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N′-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R
2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose–response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose–response (R
2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R
2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose–response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.
Sumatran megathrust earthquakes: from science to saving lives
Authors: Sieh Kerry
Published: June 2006

Most of the loss of life, property and well-being stemming from the great Sumatran earthquake and tsunami of 2004 could have been avoided and losses from similar future events can be largely prevented. However, achieving this goal requires forging a chain linking basic science—the study of why, when and where these events occur—to people's everyday lives. The intermediate links in this chain are emergency response preparedness, warning capability, education and infrastructural changes. In this article, I first describe our research on the Sumatran subduction zone. This research has allowed us to understand the basis of the earthquake cycle on the Sumatran megathrust and to reconstruct the sequence of great earthquakes that have occurred there in historic and prehistoric times. On the basis of our findings, we expect that one or two more great earthquakes and tsunamis, nearly as devastating as the 2004 event, are to be expected within the next few decades in a region of coastal Sumatra to the south of the zone affected in 2004. I go on to argue that preventing future tragedies does not necessarily involve hugely expensive or high-tech solutions such as the construction of coastal defences or sensor-based tsunami warning systems. More valuable and practical steps include extending the scientific research, educating the at-risk populations as to what to do in the event of a long-lasting earthquake (i.e. one that might be followed by a tsunami), taking simple measures to strengthen buildings against shaking, providing adequate escape routes and helping the residents of the vulnerable low-lying coastal strips to relocate their homes and businesses to land that is higher or farther from the coast. Such steps could save hundreds and thousands of lives in the coastal cities and offshore islands of western Sumatra, and have general applicability to strategies for helping the developing nations to deal with natural hazards.
Extreme events due to human-induced climate change
Authors: Mitchell John F.B , Lowe Jason , Wood Richard A , Vellinga Michael
Published: June 2006

A recent assessment by the intergovernmental panel on climate change concluded that the Earth's climate would be 2–6 °C warmer than in the pre-industrial era by the end of the twenty-first century, due to human-induced increases in greenhouse gases. In the absence of other changes, this would lead to the warmest period on Earth for at least the last 1000 years, and probably the last 100 000 years. The large-scale warming is expected to be accompanied by increased frequency and/or intensity of extreme events, such as heatwaves, heavy rainfall, storms and coastal flooding. There are also several possibilities that this large change could initiate nonlinear climate responses which lead to even more extreme and rapid (on the time-scale of decades) climate change, including the collapse of the ocean ‘conveyor belt’ circulation, the collapse of major ice sheets or the release of large amounts of methane in high latitudes leading to further global warming. Although these catastrophic events are much more speculative than the direct warming due to increased greenhouse gases, their potential impacts are great and therefore should be included in any risk assessment of the impacts of anthropogenic climate change.
Role of the Escherichia coli nitrate transport protein, NarU, in survival during severe nutrient starvation and slow growth
Authors: Clegg Stephanie J. , Jia Wenjing , Cole Jeffrey A.
Published: June 2006

Escherichia coli K-12 strains expressing either NarU or NarK as the only nitrate transport protein are both able to support nitrate-dependent anaerobic growth. The narK gene is highly expressed during anaerobic growth in the presence of nitrate, consistent with a role for NarK in nitrate transport coupled to nitrate reduction by the most active nitrate reductase encoded by the adjacent narGHJI operon. The physiological role of NarU is unknown. Reverse transcriptase PCR experiments established that, unlike the monocistronic narK gene, narU is co-transcribed with narZ as the first gene of a five-gene narUZYWV operon. The narK and narU genes were fused in-frame to a myc tag: the encoded fusion proteins complemented the nitrate-dependent growth defect of chromosomal narK and narU mutations. A commercial anti-Myc antibody was used to detect NarK and NarU in membrane fractions. During anaerobic growth in the presence of nitrate, the quantity of NarU-Myc accumulated during exponential growth was far less than that of NarK-Myc, but NarU was more abundant than NarK in stationary-phase cultures in the absence of nitrate. Although the concentration of NarU-Myc increased considerably during the post-exponential phase of growth, NarK-Myc was still more abundant than NarU-Myc in stationary-phase bacteria in the presence of nitrate. In chemostat competition experiments, a strain expressing only narU had a selective advantage relative to a strain expressing only narK during nutrient starvation or very slow growth, but NarK+ bacteria had a much greater selective advantage during rapid growth. The data suggest that NarU confers a selective advantage during severe nutrient starvation or slow growth, conditions similar to those encountered in vivo.
Molecular characterization of a conserved archaeal copper resistance (cop) gene cluster and its copper-responsive regulator in Sulfolobus solfataricus P2
Authors: Ettema Thijs J. G. , Brinkman Arie B. , Lamers Packo P. , Kornet Noor G. , de Vos Willem M. , van der Oost John
Published: June 2006

Using a comparative genomics approach, a copper resistance gene cluster has been identified in multiple archaeal genomes. The cop cluster is predicted to encode a metallochaperone (CopM), a P-type copper-exporting ATPase (CopA) and a novel, archaea-specific transcriptional regulator (CopT) which might control the expression of the cop genes. Sequence analysis revealed that CopT has an N-terminal DNA-binding helix–turn–helix domain and a C-terminal TRASH domain; TRASH is a novel domain which has recently been proposed to be uniquely involved in metal-binding in sensors, transporters and trafficking proteins in prokaryotes. The present study describes the molecular characterization of the cop gene cluster in the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The polycistronic copMA transcript was found to accumulate in response to growth-inhibiting copper concentrations, whereas copT transcript abundance appeared to be constitutive. DNA-binding assays revealed that CopT binds to the copMA promoter at multiple sites, both upstream and downstream of the predicted TATA-BRE site. Copper was found to specifically modulate the affinity of DNA binding by CopT. This study describes a copper-responsive operon in archaea, a new family of archaeal DNA-binding proteins, and supports the idea that this domain plays a prominent role in the archaeal copper response. A model is proposed for copper-responsive transcriptional regulation of the copMA gene cluster.
Functional identification of ygiP as a positive regulator of the ttdA-ttdB-ygjE operon
Authors: Oshima Taku , Biville Francis
Published: June 2006

Functional characterization of unknown genes is currently a major task in biology. The search for gene function involves a combination of various in silico, in vitro and in vivo approaches. Available knowledge from the study of more than 21 LysR-type regulators in Escherichia coli has facilitated the classification of new members of the family. From sequence similarities and its location on the E. coli chromosome, it is suggested that ygiP encodes a lysR regulator controlling the expression of a neighbouring operon; this operon encodes the two subunits of tartrate dehydratase (TtdA, TtdB) and YgiE, an integral inner-membrane protein possibly involved in tartrate uptake. Expression of tartrate dehydratase, which converts tartrate to oxaloacetate, is required for anaerobic growth on glycerol as carbon source in the presence of tartrate. Here, it has been demonstrated that disruption of ygiP, ttdA or ygjE abolishes tartrate-dependent anaerobic growth on glycerol. It has also been shown that tartrate-dependent induction of the ttdA-ttdB-ygjE operon requires a functional YgiP.
Broad-spectrum antibacterial activity by a novel abiogenic peptide mimic
Authors: Nüsslein Klaus , Arnt Lachelle , Rennie Jason , Owens Cullen , Tew Gregory N.
Published: June 2006

The human-mediated use and abuse of classical antibiotics has created a strong selective pressure for the rapid evolution of antibiotic resistance. As resistance levels rise, and the efficacy of classical antibiotics wanes, the intensity of the search for alternative antimicrobials has increased. One class of molecules that has attracted much attention is the antimicrobial peptides (AMPs). They exhibit broad-spectrum activity, they are potent and they are widespread as part of the innate defence system of both vertebrates and invertebrates. However, peptides are complex molecules that suffer from proteolytic degradation. The ability to capture the essential properties of antimicrobial peptides in simple easy-to-prepare molecules that are abiotic in origin and non-proteolytic offers many advantages. Mechanistic and structural knowledge of existing AMPs was used to design a novel compound that mimics the biochemical activity of an AMP. This report describes the development and in vitro characterization of a small peptide mimic that exhibited quick-acting and selective antibacterial activity against a broad range of bacteria, including numerous clinically relevant strains, at low MIC values.
Dysgalacticin: a novel, plasmid-encoded antimicrobial protein (bacteriocin) produced by Streptococcus dysgalactiae subsp. equisimilis
Authors: Heng Nicholas C. K. , Ragland Nancy L. , Swe Pearl M. , Baird Hayley J. , Inglis Megan A. , Tagg John R. , Jack Ralph W.
Published: June 2006

Dysgalacticin is a novel bacteriocin produced by Streptococcus dysgalactiae subsp. equisimilis strain W2580 that has a narrow spectrum of antimicrobial activity directed primarily against the principal human streptococcal pathogen Streptococcus pyogenes. Unlike many previously described bacteriocins of Gram-positive bacteria, dysgalacticin is a heat-labile 21.5 kDa anionic protein that kills its target without inducing lysis. The N-terminal amino acid sequence of dysgalacticin [Asn-Glu-Thr-Asn-Asn-Phe-Ala-Glu-Thr-Gln-Lys-Glu-Ile-Thr-Thr-Asn-(Asn)-Glu-Ala] has no known homologue in publicly available sequence databases. The dysgalacticin structural gene, dysA, is located on the indigenous plasmid pW2580 of strain W2580 and encodes a 220 aa preprotein which is probably exported via a Sec-dependent transport system. Natural dysA variants containing conservative amino acid substitutions were also detected by sequence analyses of dysA elements from S. dysgalactiae strains displaying W2580-like inhibitory profiles. Production of recombinant dysgalacticin by Escherichia coli confirmed that this protein is solely responsible for the inhibitory activity exhibited by strain W2580. A combination of in silico secondary structure prediction and reductive alkylation was employed to demonstrate that dysgalacticin has a novel structure containing a disulphide bond essential for its biological activity. Moreover, dysgalacticin displays similarity in predicted secondary structure (but not primary amino acid sequence or inhibitory spectrum) with another plasmid-encoded streptococcal bacteriocin, streptococcin A-M57 from S. pyogenes, indicating that dysgalacticin represents a prototype of a new class of antimicrobial proteins.
Cloning and expression of the gene for periplasmic poly(vinyl alcohol) dehydrogenase from Sphingomonas sp. strain 113P3, a novel-type quinohaemoprotein alcohol dehydrogenase
Authors: Hirota-Mamoto Rie , Nagai Ryoko , Tachibana Shinjiro , Yasuda Masaaki , Tani Akio , Kimbara Kazuhide , Kawai Fusako
Published: June 2006

A gene for periplasmic poly(vinyl alcohol) (PVA) dehydrogenase (PVADH) was cloned, based on the N-terminal amino acid sequence of the purified PVADH from Sphingomonas sp. 113P3 and the sequence of the gene for PVADH (pvaA, GenBank accession no. AB190288). The recombinant PVADH tagged with hexahistidine was expressed in Escherichia coli and purified to homogeneity. The recombinant enzyme had the same characteristics as the purified enzyme from Sphingomonas sp. strain 113P. In addition to PVA, the recombinant PVADH could oxidize glycols such as polypropylene glycols and 1,3-butane/cyclohexanediol and 2,4-pentanediol, but neither primary nor secondary alcohols. The amino acid sequence of the recombinant PVADH showed similarity with those of PVADH from Pseudomonas sp. strain VM15C, putative PVADHs from Azoarcus sp. EbN1, and Xanthomonas species (54–25 % identity), and the quinohaemoprotein alcohol dehydrogenases (QH-ADHs) from Comamonas testosteroni, Ralstonia eutropha and Pseudomonas putida (25–29 % identity). PVADHs from strains 113P3 and VM15C have a conserved superbarrel domain (SD), probable PQQ-binding amino acids in the SD and a haem-binding domain (HBD) (they should be designated QH-PVADHs), but the positions of the amino acid sequences for the HBD and SD are the reverse of those of QH-ADHs. A protein structure of QH-PVADHs is proposed. Results of dot-blot hybridization and RT-PCR indicated that the three genes encoding oxidized PVA hydrolase, PVADH and cytochrome c are expressed constitutively and form an operon.
Distribution of prophages and SGI-1 antibiotic-resistance genes among different Salmonella enterica serovar Typhimurium isolates
Authors: Hermans Armand P. H. M. , Beuling Annelien M. , van Hoek Angela H. A. M. , Aarts Henk J. M. , Abee Tjakko , Zwietering Marcel H.
Published: June 2006

Recently, the authors identified Salmonella enterica serovar Typhimurium (S. Typhimurium) definitive type (DT)104-specific sequences of mainly prophage origin by genomic subtractive hybridization. In the present study, the distribution of the prophages identified, ST104 and ST64B, and the novel prophage remnant designated prophage ST104B, was tested among 23 non-DT104 S. Typhimurium isolates of different phage types and 19 isolates of the DT104 subtypes DT104A, DT104B low and DT104L, and the DT104-related type U302. The four S. Typhimurium prophages Gifsy-1, Gifsy-2, Fels-1 and Fels-2 were also included. Analysis of prophage distribution in different S. Typhimurium isolates may supply additional information to enable development of a molecular method as an alternative to phage typing. Furthermore, the presence of the common DT104 antibiotic resistance genes for the penta-resistance type ACSSuT, aadA2, floR, pse-1, sul1 and tet(G), was also studied because of the authors' focus on this emerging type. Based on differences in prophage presence within their genome, it was possible to divide S. Typhimurium isolates into 12 groups. Although no clear relationship was found between different phage type and prophage presence, discrimination could be made between the different DT104 subtypes based on diversity in the presence of prophages ST104, ST104B and ST64B. The novel prophage remnant ST104B, which harbours a homologue of the Escherichia coli O157 : H7 HldD LPS assembly-related protein, was identified only in the 14 DT104L isolates and in the DT104-related U302 isolate. In conclusion, the presence of the genes for penta-resistance type ACSSuT, the HldD homologue containing ST104 prophage remnant and phage type DT104L are most likely common features of the emerging subtype of S. Typhimurium DT104.
Two novel conjugative plasmids from a single strain of Sulfolobus
Authors: Erauso Gaël , Stedman Kenneth M. , van de Werken Harmen J. G. , Zillig Wolfram , van der Oost John
Published: June 2006

Two conjugative plasmids (CPs) were isolated and characterized from the same ‘Sulfolobus islandicus’ strain, SOG2/4. The plasmids were separated from each other and transferred intoSulfolobus solfataricus. One has a high copy number and is not stable (pSOG1) whereas the other has a low copy number and is stably maintained (pSOG2). Plasmid pSOG2 is the firstSulfolobusCP found to have these characteristics. The genomes of both pSOG plasmids have been sequenced and were compared to each other and the availableSulfolobusCPs. Interestingly, apart from a very well-conserved core, 70 % of the pSOG1 and pSOG2 genomes is largely different and composed of a mixture of genes that often resemble counterparts in previously describedSulfolobusCPs. However, about 20 % of the predicted genes do not have known homologues, not even in other CPs. Unlike pSOG1, pSOG2 does not contain a gene for the highly conserved PlrA protein nor for obvious homologues of partitioning proteins. Unlike pNOB8 and pKEF9, both pSOG plasmids lack the so-called clustered regularly interspaced short palindrome repeats (CRISPRs). The sites of recombination between the two genomes can be explained by the presence of recombination motifs previously identified in otherSulfolobusCPs. Like otherSulfolobusCPs, the pSOG plasmids possess a gene encoding an integrase of the tyrosine recombinase family. This integrase probably mediates plasmid site-specific integration into the host chromosome at the highly conserved tRNAGluloci.
Methylglyoxal detoxification by an aldo-keto reductase in the cyanobacterium Synechococcus sp. PCC 7002
Authors: Xu Dongyi , Liu Xianwei , Guo Cong , Zhao Jindong
Published: June 2006

Aldo-keto reductases (AKRs) are a superfamily of enzymes that reduce aldehydes and ketones, and have a broad range of substrates. An AKR gene,sakR1, was identified in the cyanobacteriumSynechococcussp. PCC 7002. A mutant strain withsakR1inactivated was sensitive to glycerol, a carbon source that can support heterotrophic growth ofSynechococcussp. PCC 7002. It was found that thesakR1null mutant accumulated more toxic methylglyoxal than the wild-type when glycerol was added to growth medium, suggesting that SakR1 is involved in the detoxification of methylglyoxal, a highly toxic metabolite that can damage cellular macromolecules. Enzymic analysis of recombinant SakR1 protein showed that it can efficiently reduce methylglyoxal with NADPH. Based on immunoblotting, SakR1 was not upregulated at an increased cellular methylglyoxal concentration. A pH-dependent enzyme-activity profile suggested that SakR1 activity could be regulated by cellular pH inSynechococcussp. PCC 7002. The broad substrate specificity of SakR1 implies that SakR1 could play other roles in cellular metabolism.
Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence
Authors: Romano Jacob , Nimrod Guy , Ben-Tal Nir , Shadkchan Yona , Baruch Koti , Sharon Haim , Osherov Nir
Published: June 2006

The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an important role in maintaining fungal cell wall integrity and virulence. However, the precise molecular role of these proteins is unknown. In this work, AfuEcm33, the gene encoding the ECM33 homologue in the important pathogenic fungus Aspergillus fumigatus, has been cloned and its function analysed. It is shown that disruption of AfuEcm33 results in rapid conidial germination, increased cell–cell adhesion, resistance to the antifungal agent caspofungin and increased virulence in an immunocompromised mouse model for disseminated aspergillosis. These results suggest that the protein encoded by AfuEcm33 is involved in key aspects of cell wall morphogenesis and plays an important role in A. fumigatus virulence.
Characterization of genes involved in erythritol catabolism in Rhizobium leguminosarum bv. viciae
Authors: Yost Christopher K. , Rath Amber M. , Noel Tanya C. , Hynes Michael F.
Published: June 2006

A genetic locus encoding erythritol uptake and catabolism genes was identified in Rhizobium leguminosarum bv. viciae, and shown to be plasmid encoded in a wide range of R. leguminosarum strains. A Tn5-B22 mutant (19B-3) unable to grow on erythritol was isolated from a mutant library of R. leguminosarum strain VF39SM. The mutated gene eryF was cloned and partially sequenced, and determined to have a high homology to permease genes of ABC transporters. A cosmid complementing the mutation (pCos42) was identified and was shown to carry all the genes necessary to restore the ability to grow on erythritol to a VF39SM strain cured of pRleVF39f. In the genomic DNA sequence of strain 3841, the gene linked to the mutation in 19B-3 is flanked by a cluster of genes with high homology to the known erythritol catabolic genes from Brucella spp. Through mutagenesis studies, three distinct operons on pCos42 that are required for growth on erythritol were identified: an ABC-transporter operon (eryEFG), a catabolic operon (eryABCD) and an operon (deoR-tpiA2-rpiB) that encodes a gene with significant homology to triosephosphate isomerase (tpiA2). These genes all share high sequence identity to genes in the erythritol catabolism region of Brucella spp., and clustalw alignments suggest that horizontal transfer of the erythritol locus may have occurred between R. leguminosarum and Brucella. Transcription of the eryABCD operon is repressed by EryD and is induced by the presence of erythritol. Mutant 19B-3 was impaired in its ability to compete against wild-type for nodulation of pea plants but was still capable of forming nitrogen-fixing nodules.
The role of future ICT in city development
Authors: Pearson Ian
Published: June 2006

Purpose

The purpose of this article is to explore the role of information and communications technologies (ICT) in creating cities that are attractive, healthy and prosperous places to live, work and visit.

Design/methodology/approach

Considers technological developments in information and communications technologies in the short‐ and medium‐term and their application in the urban environment.

Findings

IT is developing faster than ever and will be a useful tool in the redevelopment of cities. Short‐term developments such as wireless LANs may be unglamorous but have large potential for opening up new areas of opportunities, both in social and business uses. In the mid‐term, these networks will combine with ambient intelligence to make a smart digital air overlay, making every part of a city electronically enabled. The result will be big improvement in public transport and city architecture. Other IT developments will improve health, governance and security. If managed well, future urban society will be happier, less lonely, more prosperous, healthier and more involved in decision making.

Originality/value

Offers a personal view of the ways in which advances in information technologies can make a positive contribution to urban environments over the next ten to 15 years.
Towards a clarification of probability, possibility and plausibility: how semantics could help futures practice to improve
Authors: van der Helm Ruud
Published: June 2006

Purpose

The purpose of this paper is to discuss the clarification of three qualifiers “probable”, “possible” and “plausible”, which are often used interchangeably in foresight and futures studies practice, but which could obtain added value through a careful distinction. In general, it shows the importance of language as the main tool for futures practitioners.

Design/methodology/approach

Employs semantic and conceptual research.

Findings

Distinction of the three qualifiers has not only semantic importance; it also leads to a better conception of what futures practice could work towards.

Practical implications

Futures practitioners should more carefully apply their vocabulary, since it is their main tool. By carefully distinguishing probability, possibility and plausibility, a better focus on the purpose of futures practice becomes attainable.

Originality/value

Very little effort is spent on the working of language in futures studies. Besides glossaries, there is very little work done in sharpening this major tool. The semantic confusion that reigns within the foresight/futures studies community is mainly due to a lack of involvement in this clarification process. Applied semantics is often considered as burdensome, whereas it should be at the core of how the future is being conceptualized.
Association between ADAM33 polymorphisms and adult asthma in the Japanese population
Authors: Hirota T. , Hasegawa K. , Obara K. , Matsuda A. , Akahoshi M. , Nakashima K. , Shirakawa T. , Doi S. , Fujita K. , Suzuki Y. , Nakamura Y. , Tamari M.
Published: June 2006

Background
ADAM33, a member of the ADAM (a disintegrin and metalloprotease) family, is a putative asthma susceptibility gene recently identified by positional cloning. It is important to know whether the association exists in ethnically diverse populations.

Objective
To assess whether genetic functional variants of ADAM33 relate to the susceptibility or some phenotypes in adult patients with bronchial asthma in a Japanese population.

Methods
We searched for single nucleotide polymorphisms (SNPs) in ADAM33 by PCR‐directed sequencing and identified 48 SNPs. Fourteen SNPs were selected with regard to the LD pattern, and genotyped by Taq‐Man and PCR–RFLP methods. We conducted an association study of ADAM33 with 504 adult asthmatic patients and 651 controls, and haplotype analyses of related variants were performed.

Results
Significant associations with asthma were found for the SNPs T1 (Met764Thr), T2 (Pro774Ser), S2 and V−3 (with the lowest P‐value for T1, P=0.0015; OR 0.63). We analysed the haplotype using these four polymorphisms, and found a positive association with haplotype CCTG (P=0.0024).

Conclusion
Our results replicate associations reported recently in other ethnic populations, and suggest that the ADAM33 gene is involved in the development of asthma through genetic polymorphisms.
Surfactant protein D inhibits early airway response in Aspergillus fumigatus‐sensitized mice
Authors: Erpenbeck V. J. , Ziegert M. , Cavalet‐Blanco D. , Martin C. , Baelder R. , Glaab T. , Braun A. , Steinhilber W. , Luettig B. , Uhlig S. , Hoymann H. G. , Krug N. , Hohlfeld J. M.
Published: June 2006

Background
The surfactant protein SP‐D has been reported to reduce bronchial hyper‐responsiveness, blood eosinophilia, and T‐helper type 2 cytokines in models of allergic asthma. However, little is known about the functional effect of SP‐D on the early airway response upon allergen inhalation, which is an important feature of this disease.

Objective
We investigated whether SP‐D is able to reduce the immediate allergen‐induced mediator release and the early bronchial obstruction in addition to its effects on airway inflammation and bronchial hyperresponsiveness in an Aspergillus fumigatus mouse asthma model.

Methods
A. fumigatus‐sensitized mice were treated with a recombinant fragment of human SP‐D or placebo. Lung functions were measured in orotracheally intubated, spontaneously breathing animals using body plethysmography. In addition, passively sensitized precision‐cut lung slices (PCLS) were used to determine the effect of SP‐D on allergen‐induced histamine release.

Results
SP‐D inhibited the allergen‐induced early airway response and reduced airway hyperresponsiveness compared with placebo. Eosinophilia in bronchoalveolar lavage and lung tissue was reduced after SP‐D treatment, possibly by reducing eotaxin levels in the lung. Furthermore, SP‐D treatment reduced the allergen‐induced histamine release from PCLS.

Conclusions
These data suggest that SP‐D not only reduces allergen‐induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release.
Snow depth, soil freezing, and fluxes of carbon dioxide, nitrous oxide and methane in a northern hardwood forest
Authors: GROFFMAN PETER M. , HARDY JANET P. , DRISCOLL CHARLES T. , FAHEY TIMOTHY J.
Published: June 2006

Soil–atmosphere fluxes of trace gases (especially nitrous oxide (N2O)) can be significant during winter and at snowmelt. We investigated the effects of decreases in snow cover on soil freezing and trace gas fluxes at the Hubbard Brook Experimental Forest, a northern hardwood forest in New Hampshire, USA. We manipulated snow depth by shoveling to induce soil freezing, and measured fluxes of N2O, methane (CH4) and carbon dioxide (CO2) in field chambers monthly (bi‐weekly at snowmelt) in stands dominated by sugar maple or yellow birch. The snow manipulation and measurements were carried out in two winters (1997/1998 and 1998/1999) and measurements continued through 2000. Fluxes of CO2 and CH4 showed a strong seasonal pattern, with low rates in winter, but N2O fluxes did not show strong seasonal variation. The snow manipulation induced soil freezing, increased N2O flux and decreased CH4 uptake in both treatment years, especially during winter. Annual N2O fluxes in sugar maple treatment plots were 207 and 99 mg N m−2 yr−1 in 1998 and 1999 vs. 105 and 42 in reference plots. Tree species had no effect on N2O or CO2 fluxes, but CH4 uptake was higher in plots dominated by yellow birch than in plots dominated by sugar maple. Our results suggest that winter fluxes of N2O are important and that winter climate change that decreases snow cover will increase soil:atmosphere N2O fluxes from northern hardwood forests.
GLUT1 and p63 expression in endometrial intraepithelial and uterine serous papillary carcinoma
Authors: Idrees M T , Schlosshauer P , Li G , Burstein D E
Published: June 2006

Aims : To analyse the expression patterns of GLUT1, p63 and p53 and the possible correlation between these markers in uterine serous papillary carcinoma (USPC) and endometrial intraepithelial carcinoma (EIC).

Methods and results : Fourteen cases of USPC, 12 of which also showed EIC, were examined for GLUT1, p63 and p53 immunoreactivity. Four‐micrometre sections from formalin‐fixed paraffin‐embedded tissue were immunostained using commercially available primary antibodies and Dako Envision Plus reagents for visualization. Membranous GLUT1 immunoreactivity was observed in all cases, including all 14 invasive tumours (100%) and 11 of 12 associated EICs (92%), and was confined to neoplastic cells. In USPC, staining tended to be strongest in superficial antistromal regions. p63 positivity was found in 8/14 (57%) USPCs and 9/12 (75%) associated EICs. In 11 cases p53 was overexpressed in both invasive USPC (11/14; 79%) and EIC (11/12; 92%). p53+ USPCs tended to be positive for p63, whereas p53– USPCs were also negative for p63.

Conclusions : GLUT1 is expressed in the vast majority of USPC and EIC, suggesting a biological role during the early steps of carcinogenesis in endometrial serous neoplasms. GLUT1 expression may be induced by hypoxia‐related as well as other mechanisms.
KIT immunohistochemistry and mutation status in gastrointestinal stromal tumours (GISTs) evaluated for treatment with imatinib
Authors: Loughrey M B , Trivett M , Beshay V , Dobrovic A , Kovalenko S , Murray W , Lade S , Turner H , McArthur G A , Zalcberg J , Waring P M
Published: June 2006

Aims : With the availability of effective but expensive treatment in the form of imatinib, accurate diagnosis of gastrointestinal stromal tumour (GIST) is extremely important. The aims of this study were: to describe the clinicopathological, immunohistochemical and molecular features of cases referred to a cancer centre with a possible diagnosis of GIST; to identify pitfalls in the performance and interpretation of KIT immunohistochemistry; to define the role of KIT mutation testing in making a diagnosis of GIST.

Methods and results : Morphological review, KIT immunohistochemistry and mutation testing were performed on all cases referred with a diagnosis of GIST or where the diagnosis was under serious consideration on the basis of KIT immunopositivity with a view to treating with imatinib. Thirty‐seven cases met the inclusion criteria. Of these, 26 were classified as GIST and 11 as non‐GIST. Most GISTs showed strong diffuse membranous, cytoplasmic or paranuclear KIT immunopositivity. Some non‐GISTs demonstrated patchy cytoplasmic KIT immunopositivity related to the immunohistochemical protocol used in the external laboratory, which led to erroneous diagnoses of GIST in nine (24%) cases. KIT mutations involving exons 11 or 9 were identified in 22 (88%) GISTs tested and none of the non‐GISTs.

Conclusions : An accurate diagnosis of GIST can be made on clinicopathological and immunohistochemical criteria without the need for mutational analysis in most cases, provided proper attention is paid to the immunohistochemical protocol used and, most importantly, control material. False‐positive diagnoses of GIST potentially leading to inappropriate treatment with imatinib are more common than missed diagnoses.
Metaplastic breast carcinomas are basal‐like tumours
Authors: Reis‐Filho J S , Milanezi F , Steele D , Savage K , Simpson P T , Nesland J M , Pereira E M , Lakhani S R , Schmitt F C
Published: June 2006

Aims : Recently, an immunohistochemical panel comprising antibodies against HER2, oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6 was reported to identify basal‐like breast carcinomas, as defined by cDNA microarrays. Our aim was to analyse a series of metaplastic breast carcinomas (MBCs) using this panel plus two other basal markers (CK14 and p63) and progesterone receptor (PR), to define how frequently MBCs show a basal‐like immunophenotype.

Methods and results : Sixty‐five cases were retrieved from the pathology archives of the authors' institutions and reviewed by three of the authors. Immunohistochemistry with antibodies for HER2, ER, EGFR, CK5/6, CK14 and p63 was performed according to standard methods. All but six cases (91%) showed the typical immunoprofile of basal‐like tumours (ER– and HER2–, EGFR+ and/or CK5/6+). When CK14 and p63 were added to the panel, two additional cases could be classified as basal‐like. The majority of MBCs lacked PR, except 4/19 (21%) carcinomas with squamous metaplasia.

Conclusions : Our results demonstrate that MBCs show a basal‐like phenotype, regardless of the type of metaplastic elements. Moreover, as these neoplasms frequently overexpress EGFR (57%), patients with MBC may benefit from treatment with anti‐EGFR drugs.