bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular architecture of human prion protein amyloid: A parallel, in-register β-structure
Authors: Cobb Nathan J. , Sönnichsen Frank D. , Mchaourab Hassane , Surewicz Witold K.
Published: November 2007

Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative diseases that are associated with conformational conversion of the normally monomeric and α-helical prion protein, PrP
C
, to the β-sheet-rich PrP
Sc
. This latter conformer is believed to constitute the main component of the infectious TSE agent. In contrast to high-resolution data for the PrP
C
monomer, structures of the pathogenic PrP
Sc
or synthetic PrP
Sc
-like aggregates remain elusive. Here we have used site-directed spin labeling and EPR spectroscopy to probe the molecular architecture of the recombinant PrP amyloid, a misfolded form recently reported to induce transmissible disease in mice overexpressing an N-terminally truncated form of PrP
C
. Our data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrP
C
involves major refolding of the C-terminal α-helical region. The core of the amyloid maps to C-terminal residues from ≈160–220, and these residues form single-molecule layers that stack on top of one another with parallel, in-register alignment of β-strands. This structural insight has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases, most of which are associated with point mutations in the region found to undergo a refolding to β-structure.
The transcription factor IDEF1 regulates the response to and tolerance of iron deficiency in plants
Authors: Kobayashi Takanori , Ogo Yuko , Itai Reiko Nakanishi , Nakanishi Hiromi , Takahashi Michiko , Mori Satoshi , Nishizawa Naoko K.
Published: November 2007

Iron is essential for most living organisms and is often the major limiting nutrient for normal growth. Plants induce iron utilization systems under conditions of low iron availability, but the molecular mechanisms of gene regulation under iron deficiency remain largely unknown. We identified the rice transcription factor IDEF1, which specifically binds the iron deficiency-responsive
cis
-acting element IDE1. IDEF1 belongs to an uncharacterized branch of the plant-specific transcription factor family ABI3/VP1 and exhibits the sequence recognition property of efficiently binding to the CATGC sequence within IDE1.
IDEF1
transcripts are constitutively present in rice roots and leaves. Transgenic tobacco plants expressing
IDEF1
under the control of the constitutive cauliflower mosaic virus 35S promoter transactivate IDE1-mediated expression only in iron-deficient roots. Transgenic rice plants expressing an introduced
IDEF1
exhibit substantial tolerance to iron deficiency in both hydroponic culture and calcareous soil.
IDEF1
overexpression leads to the enhanced expression of the iron deficiency-induced transcription factor gene
OsIRO2
, suggesting the presence of a sequential gene regulatory network. These findings reveal
cis
element/
trans
factor interactions that are functionally linked to the iron deficiency response. Manipulation of
IDEF1
also provides another approach for producing crops tolerant of iron deficiency to enhance food and biomass production in calcareous soils.
Gene family encoding the major toxins of lethal
Amanita
mushrooms
Authors: Hallen Heather E. , Luo Hong , Scott-Craig John S. , Walton Jonathan D.
Published: November 2007

Amatoxins, the lethal constituents of poisonous mushrooms in the genus
Amanita
, are bicyclic octapeptides. Two genes in
A. bisporigera
,
AMA1
and
PHA1
, directly encode α-amanitin, an amatoxin, and the related bicyclic heptapeptide phallacidin, a phallotoxin, indicating that these compounds are synthesized on ribosomes and not by nonribosomal peptide synthetases. α-Amanitin and phallacidin are synthesized as proproteins of 35 and 34 amino acids, respectively, from which they are predicted to be cleaved by a prolyl oligopeptidase.
AMA1
and
PHA1
are present in other toxic species of
Amanita
section
Phalloidae
but are absent from nontoxic species in other sections. The genomes of
A. bisporigera
and
A. phalloides
contain multiple sequences related to
AMA1
and
PHA1
. The predicted protein products of this family of genes are characterized by a hypervariable “toxin” region capable of encoding a wide variety of peptides of 7–10 amino acids flanked by conserved sequences. Our results suggest that these fungi have a broad capacity to synthesize cyclic peptides on ribosomes.
Technology Transfer and IPR Policy for Small and Medium Firms in South‐East Asia
1
Authors: Macdonald Stuart , Turpin Tim
Published: November 2007

In theory, small and medium firms have much to gain from the intellectual property rights system: in practice, SMEs have trouble using the IPR system. Yet the developing world is encouraged by the developed to look to IPR to make its SMEs more innovative and hence competitive. If SMEs are to make effective use of IPR, it must be within their existing business strategy. For them, copying may be a more appropriate and successful form of technology transfer than licensing IPR from developed countries.
Community Mental Health Services as a Process Innovation: Appropriate Economic Evaluation
Authors: Williams Ruth F. G.
Published: November 2007

This article considers the relevant framework for evaluating a major process innovation in mental health services, viz. community‐based service provision. Such services involve multiple inputs from various channels (or departments) in government and ‘the community’. Conventional economic theory of production is extended here to incorporate the notion that economic transactions are embedded in social relations, i.e. social capital is relevant to community‐based service provision. Another fertile concept is that of ‘co‐production’, due to Elinor Ostrom, a political scientist. Ostrom’s conception of co‐production between government and community inputs is outlined in the context of mental health services. A relevant question for evaluating this process innovation emerges from the co‐production framework: is social capital from government a substitute for, or complementary to, social capital from community sources?
‘Broncoing’: A Uniquely Australian Cattle‐Handling Technology
Authors: Lewis Darrell
Published: November 2007

The early Anglo‐Celtic settlers in Australia arrived with a ‘cattle‐culture’ developed in Britain over many centuries, but their cattle‐handling technology proved inadequate for the unique conditions of Australia and new methods were soon devised. For most of the nineteenth century these new techniques required the use of a yard, but eventually the ‘bronco’ method was developed which did not require a yard and which involved a specially constructed ‘bronco panel’ and the use of a lasso thrown by a mounted horseman. This new method became the dominant cattle‐handling technique in the outback for nearly a century and is still practised on a small number of cattle stations.
Triple bypass: complicated paths to HIV escape
Authors: McMichael Andrew J.
Published: November 2007

Human immunodeficiency virus (HIV) type 1 is highly efficient at evading immune responses and persisting, ultimately causing fatal immunodeficiency in some patients. Mutation in the epitopes recognized by cytolytic CD8+ T cells (CTLs) is one such escape process. A new study now shows that one HIV-1 escape mutation may also result in impaired dendritic cell (DC) activity, possibly impairing later T cell responses to the same and other epitopes. The new data complete our understanding of the mechanisms by which the CTL response to an immunodominant gag epitope presented by human histocompatibility leukocyte antigen (HLA)-B27 is evaded. The complexity of the full escape helps to explain why patients with this HLA type progress to AIDS more slowly than average.
MANTIS: a phylogenetic framework for multi-species genome comparisons
Authors: Tzika Athanasia C. , Helaers Raphaël , Van de Peer Yves , Milinkovitch Michel C.
Published: November 2007

Motivation: Practitioners of comparative genomics face huge analytical challenges as whole genome sequences and functional/expression data accumulate. Furthermore, the field would greatly benefit from a better integration of this wealth of data with evolutionary concepts.

Results: Here, we present MANTIS, a relational database for the analysis of (i) gains and losses of genes on specific branches of the metazoan phylogeny, (ii) reconstructed genome content of ancestral species and (iii) over- or under-representation of functions/processes and tissue specificity of gained, duplicated and lost genes. MANTIS estimates the most likely positions of gene losses on the true phylogeny using a maximum-likelihood function. A user-friendly interface and an extensive query system allow to investigate questions pertaining to gene identity, phylogenetic mapping and function/expression parameters.

Availability: MANTIS is freely available at http://www.mantisdb.org and constitutes the missing link between multi-species genome comparisons and functional analyses.

Contact: mcmilink@ulb.ac.be

Supplementary information: Supplementary data are available at Bioinformatics online.
Scenario testing of fisheries management strategies using a high resolution ERSEM–POM ecosystem model
Authors: Petihakis G. , Smith C. J. , Triantafyllou G. , Sourlantzis G. , Papadopoulou K-N. , Pollani A. , Korres G.
Published: November 2007

Petihakis, G., Smith, C. J., Triantafyllou, G., Sourlantzis, G., Papadopoulou, K-N., Pollani, A., and Korres, G. 2007. Scenario testing of fisheries management strategies using a high resolution ERSEM–POM ecosystem model. – ICES Journal of Marine Science, 64: 1627–1640.

Ecosystem models are just beginning to be considered as management tools. In terms of fishery impacts, dynamic ecosystem models provide an opportunity to make advances because they can both evaluate the state of the system and make predictions about the ecosystem under various fishing scenarios. In the framework of the Cost Impact project, a complex high-resolution (500 × 500 m grid) ecosystem model was implemented in Iraklion Bay, Crete. Several management scenarios were simulated to investigate the impacts of trawling on this particular ecosystem (reductions in fishing area, effort, and mortality). Introducing trawling impacts into the model led to increases in pelagic production. All scenarios also resulted in net increases in pelagic production, the level of which, and the degree of spatial variability, was dependent on the particular scenario. Changes in pelagic variables were often noted in areas well away from trawled areas. It was also clear that for pelagic variables and processes, depth of trawling is more important than reduction in trawling area, i.e. a scenario banning fishing in waters shallower than 100 m seems to lead to less change in the pelagic system than a scenario that reduces direct mortality to the benthos.
Metal-to-insulator transition and superconductivity in boron-doped diamond
Authors: Bustarret E , Achatz P , Sacépé B , Chapelier C , Marcenat C , Ortéga L , Klein T
Published: November 2007

The experimental discovery of superconductivity in boron-doped diamond came as a major surprise to both the diamond and the superconducting materials communities. The main experimental results obtained since then on single-crystal diamond epilayers are reviewed and applied to calculations, and some open questions are identified. The critical doping of the metal-to-insulator transition (MIT) was found to coincide with that necessary for superconductivity to occur. Some of the critical exponents of the MIT were determined and superconducting diamond was found to follow a conventional type II behaviour in the dirty limit, with relatively high critical temperature values quite close to the doping-induced insulator-to-metal transition. This could indicate that on the metallic side both the electron–phonon coupling and the screening parameter depend on the boron concentration. In our view, doped diamond is a potential model system for the study of electronic phase transitions and a stimulating example for other semiconductors such as germanium and silicon.
A mechanism for crystal twinning in the growth of diamond by chemical vapour deposition
Authors: Butler James E , Oleynik Ivan
Published: November 2007

A model for the formation of crystal twins in chemical vapour deposited diamond materials is presented. The twinning mechanism originates from the formation of a hydrogen-terminated four carbon atom cluster on a local {111} surface morphology, which also serves as a nucleus to the next layer of growth. Subsequent growth proceeds by reaction at the step edges with one and two carbon atom-containing species. The model also provides an explanation for the high defect concentration observed in 〈111〉 growth sectors, the formation of penetration and contact twins, and the dramatic enhancement in polycrystalline diamond growth rates and morphology changes when small amounts of nitrogen are added to the plasma-assisted growth environments.
Unlocking diamond's potential as an electronic material
Authors: Balmer R.S , Friel I , Woollard S.M , Wort C.J.H , Scarsbrook G.A , Coe S.E , El-Hajj H , Kaiser A , Denisenko A , Kohn E , Isberg J
Published: November 2007

In this paper, we review the suitability of diamond as a semiconductor material for high-performance electronic applications. The current status of the manufacture of synthetic diamond is reviewed and assessed. In particular, we consider the quality of intrinsic material now available and the challenges in making doped structures suitable for practical devices. Two practical applications are considered in detail. First, the development of high-voltage switches capable of switching voltages in excess of 10 kV. Second, the development of diamond MESFETs for high-frequency and high-power applications. Here device data are reported showing a current density of more than 30 mA mm
−1
along with small-signal RF measurements demonstrating gigahertz operation. We conclude by considering the remaining challenges which will need to be overcome if commercially attractive diamond electronic devices are to be manufactured.
Raman spectroscopy as a probe of graphene and carbon nanotubes
Authors: Dresselhaus M.S , Dresselhaus G , Hofmann M
Published: November 2007

Progress in the use of Raman spectroscopy to characterize graphene samples for the number of graphene layers and doping level they contain is briefly reviewed. Comparisons to prior studies on graphites and carbon nanotubes are used for inspiration to define future promising directions for Raman spectroscopy research on few layer graphenes.
Weak localization in monolayer and bilayer graphene
Authors: Horsell D.W , Tikhonenko F.V , Gorbachev R.V , Savchenko A.K
Published: November 2007

We demonstrate quantitative experimental evidence for a weak localization correction to the conductivity in monolayer and bilayer graphene systems. We show how inter- and intra-valley elastic scattering control the correction in small magnetic fields in a way which is unique to graphene. A clear difference in the forms of the correction is observed in the two systems, which shows the importance of the interplay between the elastic scattering mechanisms and how they can be distinguished. Our observation of the correction at zero-net carrier concentration in both systems is clear evidence of the inhomogeneity engendered into the graphene layers by disorder.
High D‐dimer level is associated with increased 15‐d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity
Authors: Klok F. A. , Djurabi R. Karami , Nijkeuter M. , Eikenboom H. C. J. , Leebeek F. W. G. , Kramer M. H. H. , Kaasjager K. , Kamphuisen P. W. , Büller H. R. , Huisman M. V.
Published: November 2007

High D‐dimer levels are predictors of death in patients with pulmonary embolism (PE), as are more proximally located, larger emboli. The direct link between these three has not yet been described. A cohort of 674 consecutive patients with confirmed PE was studied. Patients were followed up for 3 months. D‐dimer levels were measured only in patients with an unlikely clinical probability (n = 262). The odds ratio (OR) for death of all variables was calculated. Multivariate analysis was performed to identify independent risk factors for mortality. The best predictive D‐dimer cut‐off point for mortality was a concentration >3000 ng/ml FEU (OR 7·29). High D‐dimer levels were correlated with active malignancy and age over 65 years, both being indicators of 3‐month mortality. High D‐dimer levels were also correlated with centrally located pulmonary emboli and 15‐d mortality. The combination of high D‐dimer levels and central emboli increased early mortality risk by 2·2. High D‐dimer levels in patients with an unlikely clinical probability were associated with fatal outcome after PE. Centrally located pulmonary emboli were associated with higher D‐dimer levels and worse 15‐d mortality. Active malignancy, being an inpatient at time of diagnosis and age over 65 years were associated with higher D‐dimer levels and worse 3‐month survival.
Parenting children requiring complex care: a journey through time
Authors: MacDonald H. , Callery P.
Published: November 2007

Background  Parents of children requiring complex care provide intense and demanding care in their homes. Unlike professionals who provide similar care in institutions, parents may not receive regular breaks from care giving. As a result, parents, over time, experience health and social consequences related to care giving. Respite care, one form of a break from care giving, is frequently cited as an unmet need by such parents.

Method  Given the paucity of literature on the impact of care giving over time, an ethnographic approach that involved in‐depth interviews, participant observation, eco‐maps, and document review was used. Parents of children requiring complex care, nurses and social workers participated in the study.

Results  A developmental map of care giving over time was constructed from the parents' retrospective accounts of parenting a child requiring complex care. The developmental map describes the trajectory of care for the children from infancy through young adulthood and the parents' evolving needs for respite care.

Conclusion  Existing literature focuses on the day‐to‐day experiences of parents, who are carers, rather than their experiences over time. As parents of children requiring complex care are providing care from infancy through the death of either child or parent, respite needs will change. This developmental map identifies how a group of parents reported these changes in care giving and their perceived needs for respite care.
Emotional processing in children with conduct problems and callous/unemotional traits
Authors: Woodworth M. , Waschbusch D.
Published: November 2007

Background  A considerable body of evidence now suggests that conduct problem (CP) children with callous/unemotional (CU) traits differ in many ways from CP children without these characteristics. Previous research has suggested that there are important differences for youth with CP and CU characteristics in their ability to process emotional information. The current study investigated the ability of children with disruptive behaviour disorders to label emotional faces and stories.

Methods  Participants (aged 7–12) were involved in a summer day treatment and research programme for children with disruptive behaviour problems. Two tasks were administered that were designed to measure participant's ability to recognize and label facial expressions of emotion, as well as their ability to label emotions in hypothetical situations.

Results  Results indicated that children with higher levels of CU traits, regardless of whether they had elevated CP scores, were less accurate in identifying sad facial expressions. Interestingly, children with higher CU scores were more accurate in labelling fear than were children with lower CU scores, while children with high CP but low CU traits were less accurate than other children in interpreting fearful facial emotions. Further, children's recognition of various emotional vignettes was not associated with CP, CU traits or their interaction.

Conclusions  The current study demonstrated that it was the combination of CP and a high number of CU traits that differentiated emotional attributions. Consistent with previous research, youth with CU traits had more difficulty in identifying sad facial expressions. However, contrasting with some previous studies, higher CU traits were associated with more accurate perceptions of fearful expressions. It is possible that there is something specific to fear recognition for individuals with more psychopathic, CU traits that actually make them more successful for observing or recognizing fearful expressions. Additional research is needed to clarify both the recognition and processing of fear expression in CP children with and without CU.
Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study
Authors: Hill D. J. , Hosking C. S. , De Benedictis F. M. , Oranje A. P. , Diepgen T. L. , Bauchau V. ,   the EPAAC Study Group
Published: November 2007

Background
Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE‐FS) that are commonly associated with IgE food allergy.

Objectives
To explore the relationship between high levels of IgE‐FS and AE in a large cohort of young children with eczema participating in a multi‐centre, international study.

Methods
Two thousand one hundred and eighty‐four subjects (mean age 17.6 months, range 11.8–25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP‐FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP‐FEIA levels exceeded previously reported age‐specific cut‐off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high‐risk IgE‐FS (HR‐IgE‐FS).

Results
Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR‐IgE‐FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR‐IgE‐FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset‐age <3 months had HR‐IgE‐FS.

Conclusion
Early‐onset severe eczema in infancy was associated with HR‐IgE‐FS.

Clinical implications
Food allergies should be routinely assessed in infants with moderate or severe eczema.

Capsule summary
In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE‐FS.
Leukotriene D4‐induced, epithelial cell‐derived transforming growth factor β1 in human bronchial smooth muscle cell proliferation
Authors: Bossé Y. , Thompson C. , McMahon S. , Dubois C. M. , Stankova J. , Rola‐Pleszczynski M.
Published: November 2007

BackgroundCysteinyl‐leukotrienes (cys‐LTs) orchestrate many pathognomonic features of asthma in animal models of allergic airway inflammation, including bronchial smooth muscle cell (BSMC) hyperplasia. However, because cys‐LTs alone do not induce mitogenesis in monocultures of human BSMC, the effect observedin vivoseemingly involves indirect mechanisms, which are still undefined.

ObjectiveThis study aims to investigate the regulatory role of leukotriene (LT)D4on TGF‐β1 expression in airway epithelial cells and the consequence of this interplay on BSMC proliferation.

MethodsHEK293 cells stably transfected with cys‐LT receptor 1 (CysLT1) (293LT1) were stimulated with LTD4and TGF‐β1 mRNA and protein expression was measured using Northern blot and ELISA, respectively. Conditioned medium (CM) harvested from LTD4‐treated cells was then assayed for its proliferative effect on primary human BSMC. TGF‐β1 mRNA expression was also determined in tumoural type II pneumocytes A549 and in normal human bronchial epithelial cells (NHBE) following LTD4stimulation.

ResultsThe results demonstrated that LTD4‐induced TGF‐β1 mRNA production in a time‐ and concentration‐dependent manner in 293LT1. TGF‐β1 secretion was also up‐regulated and CM from LTD4‐treated 293LT1 was shown to increase BSMC proliferation in a TGF‐β1‐dependent manner. The increased expression of TGF‐β1 mRNA by LTD4also occured in A549 and NHBE cells via a CysLT1‐dependent mechanism.

ConclusionIn conclusion, elevated expression of cys‐LTs in asthmatic airways might contribute to BSMC hyperplasia and concomitant clinical features of asthma such as airway hyperresponsiveness via a paracrine loop involving TGF‐β1 production by airway epithelial cells.
Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20‐year follow‐up study
Authors: Pesonen M. , Ranki A. , Siimes M. A. , Kallio M. J. T.
Published: November 2007

Background
Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries.

Objective
We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence.

Methods
A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re‐examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high‐ and low‐density lipoprotein cholesterol.

Results
Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non‐atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward.

Conclusion
The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy‐related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding.
Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients
Authors: Porsbjerg C. , Brannan J. D , Anderson S. D , Backer V.
Published: November 2007

Background
Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect airway inflammation more closely compared with AHR measured by stimuli that act directly on BSM.

Methods
Fifty‐three adult non‐smoking asthmatics (28 females, 18–56 years) who were not taking inhaled steroids were challenged with mannitol (up to 635 mg) and methacholine (up to 8 μmol). Induced sputum eosinophils, exhaled nitric oxide (eNO), peak flow variation and clinical severity of asthma according to the Global Initiative for Asthma guidelines were measured in addition to the health‐related quality‐of‐life score using the Juniper asthma quality‐of‐life questionnaire.

Findings
Both AHR to mannitol as well as to methacholine was associated with elevated markers of airway inflammation: in 83% of asthma patients with AHR to mannitol, and in 88% of asthma patients with AHR to methacholine, the eNO level was >20 p.p.b. Sputum% eosinophils >1% was measured in 70% of asthma patients with AHR to mannitol and in 77% of asthma patients with AHR to methacholine. In asthma patients without AHR, 15% had an eNO level >20 p.p.b., but none had sputum% eosinophils >1%. AHR to mannitol was more closely associated with the percentage of sputum eosinophils (PD15 to mannitol vs. sputum% eosinophils: r: −0.52, P<0.05), compared with AHR to methacholine (PD20 to methacholine vs. sputum% eosinophils: r: −0.28, NS). Furthermore, there was a stronger correlation between AHR to mannitol and the level of eNO [PD15 to mannitol vs. eNO (p.p.b.): r: −0.63, P<0.001], compared with AHR to methacholine [PD20 to methacholine vs. eNO (p.p.b.): r: −0.43, P<0.05].

Interpretation
In asthma patients not being treated with steroids, AHR to mannitol and to methacholine indicated the presence of airway inflammation. AHR to mannitol reflected the degree of airway inflammation more closely when compared with methacholine.
Using conservation value to assess land restoration and management alternatives across a degraded oak savanna landscape
Authors: Grundel Ralph , Pavlovic Noel B
Published: November 2007

Managers considering restoration of landscapes often face a fundamental challenge – what should be the habitat composition of the restored landscape? We present a method for evaluating an important conservation trade‐off inherent in making that decision.

Oak savannas and grasslands were historically widespread across central North America but are now rare. Today, in north‐west Indiana, USA, habitats spanning a range of woody vegetation density, from nearly treeless open habitats to forests, occur across the conserved landscape where savannas probably once dominated. To understand the benefits of different potential landscape compositions, we evaluated how different proportions of five habitats – open, savanna, woodland, scrub and forest – might affect the conservation value of the north‐west Indiana landscape for birds. Two variables of potential conservation importance were examined: species diversity, a measure of avian community richness, and conservation index, the percentage of a bird species’ global population occurring on a hectare of landscape, summed across all bird species present. Higher values of conservation index were associated with higher local densities of globally more rare and more threatened species.

Conservation index and species diversity were correlated negatively across hypothetical landscapes composed of different proportions of the five habitats. Therefore, a management trade‐off existed between conservation index and species diversity because landscapes that maximized species diversity differed from landscapes that maximized conservation index.

A landscape of 50% open, 22% savanna, 15% scrub and 13% forest was predicted to represent a compromise at which conservation index and species diversity reached the same percentage of their maxima. In contrast, the current landscape is dominated by forest.

Synthesis and applications. We quantified the trade‐off between two potential aspects of a landscape's conservation value for birds – the landscape's ability to promote avian species diversity and the landscape's use by threatened avian species. This quantification allowed us to evaluate the ability of different landscape compositions to achieve preferable trade‐off compromises, such as maximizing diversity for a given level of landscape use by threatened species. Managers can use these trade‐off results to determine which landscape compositions are associated with particular conservation and management priorities.
Role of intracellular kinases in the regulation of equine eosinophil migration and actin polymerization
Authors: WESTON M. C. , COLLINS M. E. , CUNNINGHAM F. M.
Published: November 2007

Inappropriately activated eosinophils can contribute to disease pathogenesis and intracellular signalling pathways that regulate functional responses may represent a therapeutic target. Little is known about intracellular signalling in equine eosinophils and this study examined the role of phospholipase C (PLC) and a range of protein kinases on responses to histamine and CCL11. Histamine (10−4 m) or CCL11 (5.6 × 10−9 m)‐induced actin polymerization, migration and superoxide production by eosinophils from healthy horses were compared in the presence and absence of selective kinase inhibitors. Inhibition of phosphatidylinositol‐3 kinase (PI3K) significantly reduced the response in each assay. In contrast, whilst inhibition of PLC decreased actin polymerization and superoxide production, an increase in migration was observed; the latter effect was also seen when protein kinase C (PKC) was inhibited. With the exception of histamine‐induced migration, which was significantly reduced by blocking extracellular regulated kinase (ERK)1/2, activation of ERK1/2, p38 MAPK and tyrosine kinase did not appear to play an important role in the responses studied. These results suggest that equine eosinophil activation by histamine and CCL11 is mediated through PI3K. Whilst PLC activation is required for actin polymerization and superoxide production, migration may be negatively regulated by PLC and PKC. These kinases represent potential targets for modulating eosinophil activation by multiple stimuli.
The DNA nucleoid‐associated protein Fis co‐ordinates the expression of the main virulence genes in the phytopathogenic bacterium Erwinia chrysanthemi
Authors: Lautier Thomas , Nasser William
Published: November 2007

Erwinia chrysanthemi strain 3937 is a necrotrophic bacterial plant pathogen. Pectinolytic enzymes and, in particular, pectate lyases (Pels) play a key role in soft rot symptoms but the efficient colonization of plants by E. chrysanthemi requires additional factors. These factors include the harpin HrpN, the cellulase Cel5, proteases (Prts), flagellar proteins and the Sap system, involved in the detoxification of plant antimicrobial peptides. HrpN and flagellum are mostly involved in the early steps of infection whereas the degradative enzymes (Pels, Cel5, Prts) are mainly required in the advanced stages. Production of these virulence factors is tightly regulated by environmental conditions. This report shows that the nucleoid‐associated protein Fis plays a pivotal role in the expression of the main virulence genes. Its production is regulated in a growth phase‐dependent manner and is under negative autoregulation. An E. chrysanthemi fis mutant displays a reduced motility and expression of hrpN, prtC and the sap operon. In contrast, the expression of the cel5 gene is increased in this mutant. Furthermore, the induction of the Pel activity is delayed and increased during the stationary growth phase in the fis mutant. Most of these controls occur through a direct effect because purified Fis binds to the promoter regions of fis, hrpN, sapA, cel5 and fliC. Moreover, potassium permanganate footprinting and in vitro transcription assays have revealed that Fis prevents transcription initiation at the fis promoter and also transcript elongation from the cel5 promoter. Finally, the fis mutant has a decreased virulence. These results suggest a co‐ordinated regulation by Fis of virulence factors involved in certain key steps of infection, early (asymptomatic) and advanced (symptomatic) phases.
Ternary complex formation between AmtB, GlnZ and the nitrogenase regulatory enzyme DraG reveals a novel facet of nitrogen regulation in bacteria
Authors: Huergo Luciano F. , Merrick Mike , Pedrosa Fábio O. , Chubatsu Leda S. , Araujo Luíza M. , Souza Emanuel M.
Published: November 2007

Ammonium movement across biological membranes is facilitated by a class of ubiquitous channel proteins from the Amt/Rh family. Amt proteins have also been implicated in cellular responses to ammonium availability in many organisms. Ammonium sensing by Amt in bacteria is mediated by complex formation with cytosolic proteins of the PII family. In this study we have characterized in vitro complex formation between the AmtB and PII proteins (GlnB and GlnZ) from the diazotrophic plant‐associative bacterium Azospirillum brasilense. AmtB–PII complex formation only occurred in the presence of adenine nucleotides and was sensitive to 2‐oxoglutarate when Mg2+ and ATP were present, but not when ATP was substituted by ADP. We have also shown in vitro complex formation between GlnZ and the nitrogenase regulatory enzyme DraG, which was stimulated by ADP. The stoichiometry of this complex was 1:1 (DraG monomer : GlnZ trimer). We have previously reported that in vivo high levels of extracellular ammonium cause DraG to be sequestered to the cell membrane in an AmtB and GlnZ‐dependent manner. We now report the reconstitution of a ternary complex involving AmtB, GlnZ and DraG in vitro. Sequestration of a regulatory protein by the membrane‐bound AmtB–PII complex defines a new regulatory role for Amt proteins in Prokaryotes.
Regulation of nitrate reductase by nitric oxide in Chinese cabbage pakchoi (Brassica chinensis L.)
Authors: DU SHAOTING , ZHANG YONGSONG , LIN XIANYONG , WANG YUE , TANG CAIXIAN
Published: November 2007

Nitrate reductase (NR), a committed enzyme in nitrate assimilation, involves generation of nitric oxide (NO) in plants. Here we show that the NR activity was significantly enhanced by the addition of NO donors sodium nitroprusside (SNP) and NONOate (diethylamine NONOate sodium) to the culturing solution, whereas it was decreased by NO scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide (cPTIO). Interestingly, both NO gas and SNP directly enhanced but cPTIO inhibited the NR activities of crude enzyme extracts and purified NR enzyme. The cPTIO terminated the interaction between NR‐generated NO and the NR itself. Furthermore, the NR protein content was not affected by the SNP treatment. The investigation of the partial reactions catalysed by purified NR using various electron donors and acceptors indicated that the haem and molybdenum centres in NR were the two sites activated by NO. The results suggest that the activation of NR activity by NO is regulated at the post‐translational level, probably via a direct interaction mechanism. Accordingly, the concentration of nitrate both in leaves and roots was decreased after 2 weeks of cultivation with SNP. The present study identifies a new mechanism of NR regulation and nitrate assimilation, which provides important new insights into the complex regulation of N‐metabolism in plants.
Survival of Tilletia indica teliospores under European soil conditions
Authors: Inman A. , Magnus H. A. , Riccioni L. , Hughes K. , Coates M. , Barnes A. , Barton V. , Sansford C. , Valvassori M. , Di Giambattista G. , Porta‐Puglia A. , Razzaghian J. , Peterson G.
Published: November 2007

As part of developing a European Pest Risk Analysis (PRA) for Tilletia indica, the causal agent of Karnal bunt of wheat, teliospore survival studies were done outside under quarantine containment at three European sites (Norway, UK, Italy). At each site, experiments were set up in three consecutive years (Experiments 1, 2 & 3) to determine teliospore survival over time (1–3 years) at 5, 10 and 20 cm depths. Experiments were sampled annually and survival assessed in relation to teliospore recovery and to germination at recovery (T0) and 3 months after recovery in case of burial‐induced dormancy (T3). Teliospores survived at all three sites at all depths over all the time periods studied. At each site, there was no evidence of a marked decline in teliospore recovery between sampling years, except in one set of years in one Norwegian experiment. There was no consistent effect of depth on recovery. In general there was little evidence for a marked decline in teliospore germination between sampling years. There was some evidence of a decrease in germination with increasing depth in the UK, and for some time‐depth interactions. After 3 years’ incubation (Experiment 1), mean teliospore recovery and mean germination were: UK: 61% recovery and 31% (33%) germination for T0 (and T3); Italy: 30% recovery and 36% (29%) germination; and Norway: 12% recovery and 19% (49%) germination. Germination for laboratory controls ranged from 20–59% (UK), 18–41% (Italy) and 28–59% (Norway). There was no evidence for burial‐induced dormancy except in Norway. Teliospores of T. indica can survive for at least three years in European soils. This prolonged period of survival could support establishment of the pathogen if it were introduced into areas of European cereal production.
A Novel Modification of a Flow Cytometric Assay of Phosphorylated STAT1 in Whole Blood Monocytes for Immunomonitoring of Patients on IFNα Regimen
Authors: Vakkila J. , Nieminen U. , Siitonen S. , Turunen U. , Halme L. , Nuutinen H. , Mustonen H. , Puolakkainen P. , Färkkilä M. , Repo H.
Published: November 2007

We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)α regimen. CD14+ monocytes responded strongly to IFNα/γ being sensitive indicators for recent immune activation. At 45 min after s.c. IFNα 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long‐term deficient phosphorylated STAT1 response to IFNαin vitro that in patients on standard IFNα regimen lasted for 48 h. In patients on pegylated IFNα the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.
Critical Role of Qa1b in the Protection of Mature Dendritic Cells from NK Cell‐Mediated Killing
Authors: Persson C. M. , Assarsson E. , Vahlne G. , Brodin P. , Chambers B. J.
Published: November 2007

Molecular interactions in natural killer (NK) cell‐mediated killing of dendritic cells (DC) have under recent years come under scrutiny. Upon stimulation with IFN‐γ or lipopolysaccharide, DC become relatively resistant to NK cell‐mediated lysis. In the present study, we investigated the role of Qa1b on DC and its receptor NKG2A on NK cells in the protection of mature DC from NK cells. We demonstrate that while both NKG2A+ and NKG2A‐ NK cells can efficiently lyse unstimulated DC, NKG2A+ NK cells but not NKG2A‐ NK cells are largely impaired in their ability to lyse mature DC. Similarly, mature DC from mice expressing H‐2Db, whose leader peptide sequence binds and stabilizes Qa1b, were resistant to NK cell‐mediated killing, suggesting that stable Qa1b expression contributes to the protection of mature DC. This finding was further validated by the demonstration that addition of the Qdm leader peptide could protect TAP1‐/‐ DC from NK cell‐mediated lysis both in vitro and in vivo. The present data suggest that stable expression of Qa1 on the surface of mature DC contributes to the protection of DC from NK cell‐mediated lysis.
Alterations in Antral Cytokine Gene Expression in Peptic Ulcer Patients During Ulcer Healing and After Helicobacter pylori Eradication
Authors: Goll R. , Cui G. , Olsen T. , Isaksen V. , Gruber F. , Husebekk A. , Florholmen J.
Published: November 2007

Earlier studies have shown that the antral immune response in Helicobacter pylori infection has a mixed Th1‐Th2‐T‐regulatory profile. After eradication, a chronic inflammation remains in some patients, but a follow‐up study with a comprehensive cytokine profile in has not previously been published. Twelve patients with H. pylori positive peptic ulcer disease (five antral and seven duodenal) were enrolled and cytokine gene expressions in antral biopsies were determined (1) at entry, (2) after resolving the ulcer with proton pump inhibitor (PPI) treatment and (3) after eradication. The second endoscopy was performed 4 weeks after ending the PPI treatment, and the third endoscopy was performed after a mean of 10 months after eradication. Inflammation was graded according to the updated Sydney system. Interleukin (IL)1β, IL8, IL12A, IL18, TNFα, IFNγ, IL4, IL6 and IL10 expression levels were analysed by real‐time RT‐PCR. Mixed mononuclear and neutrophil infiltrates were seen at entry and after ulcer healing. After eradication, low‐grade mononuclear infiltrates were found. The cytokine expression levels after ulcer healing (H. pylori positive gastritis) were not significantly different from the levels at entry (ulcer). After eradication, attenuation of the Th1 cytokines except for TNFα and a persisting increase of IL4 levels were observed, whereas the IL10 expression was markedly reduced. The present data did not indicate a specific ulcer promoting cytokine gene regulation profile. However, after eradication a chronic low‐grade inflammation was seen with reduced Th1, prolonged Th2 and disappearance of the T‐regulatory response.
Ediacaran in Uruguay: palaeoclimatic and palaeobiological implications
Authors: PECOITS ERNESTO , GINGRAS MURRAY , AUBET NATALIE , KONHAUSER KURT
Published: November 2007

The Ediacaran to lowermost Cambrian successions of south‐eastern Uruguay preserve an unusual and significant record of deposits generated during the Gondwana assembly (ca 590 to 535 Ma). This study presents a review of data obtained through extensive field‐based mapping coupled with detailed sedimentology and stratigraphy of key formations. The geological units within the study area consist of the Maldonado Group (Playa Hermosa, Las Ventanas and San Carlos formations), the Arroyo del Soldado Group (Yerbal, Polanco Limestones, Barriga Negra and Cerro Espuelitas formations) and the Arroyo de la Pedrera Group (Piedras de Afilar and Cerro Victoria formations). The Maldonado Group is characterized by a glacially influenced volcanogenic‐sedimentary sequence with ice‐rafted debris and dropstones in the Playa Hermosa and Las Ventanas formations. The Arroyo del Soldado Group is a mixed siliciclastic‐carbonate succession, mainly represented by an intercalation of basal pink dolostones, banded siltstones, rhythmites of dolostone‐limestone, iron formations, cherts and conglomerates. Carbonates in the Polanco Limestones Formation are characterized by a negative δ13C excursion up to −3·26‰ PeeDeeBelemnite. The Arroyo de la Pedrera Group consists of quartz arenites and stromatolitic/oolitic dolostones. Preliminary data indicate that the Precambrian–Cambrian could be contained within or at the base of this group. The entire succession is almost 6000 m thick, and contains a rich fossil assemblage composed of organic‐walled microfossils and small shelly fauna, including the index fossil Cloudina riemkeae. The stratigraphic and chemostratigraphic features are suggestive of a Gaskier age (ca 580 Ma) for the basal glacial‐related units. In this scenario, the results show the importance of lithostratigraphic, biostratigraphic and chemostratigraphic data of these Ediacaran units in the global correlation of terminal Proterozoic sedimentary rocks.
The level of matrix metalloproteinase‐2 in donor plasma strongly correlates with post‐transfusion recovery of stored platelet concentrates
Authors: Mutlu A. , Allen D. J. , Freedman J. , Leytin V.
Published: November 2007

Background and Objective  A simple test accurately predicting post‐transfusion recovery of stored platelet concentrates (PCs) is needed.

Materials and Methods  Matrix metalloproteinase‐2 (MMP‐2) was determined in fresh‐frozen plasma of normal donors using enzyme‐linked immunosorbent assay (ELISA)‐based assay. Post‐transfusion recovery of human PCs was determined in rabbits with an inhibited reticuloendothelial system by flow cytometry.

Results  We demonstrated a strong positive (r = 0·91) and highly significant (P = 0·0015) correlation between the concentration of MMP‐2 in plasma of normal donors and post‐transfusion recovery of PCs stored for 5 days at 22 °C under standard blood banking conditions. A higher level of donor plasma MMP‐2 is associated with improved recovery of transfused platelets.

Conclusion  These observations suggest that pre‐transfusion MMP‐2 assay of donor's plasma may be a predictor of post‐transfusion recovery of PCs. However, the usefulness of this assay should be elucidated in clinical transfusion settings.