bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative estimation of effective population sizes and temporal gene flow in two contrasting population systems
Authors: FRASER DYLAN J. , HANSEN MICHAEL M. , ØSTERGAARD SIRI , TESSIER NATHALIE , LEGAULT MICHEL , BERNATCHEZ LOUIS 
Published: August 2007

AbstractEstimation of effective population sizes (Ne) and temporal gene flow (Nem, m) has many implications for understanding population structure in evolutionary and conservation biology. However, comparative studies that gauge the relative performance of Ne, Nem or m methods are few. Using temporal genetic data from two salmonid fish population systems with disparate population structure, we (i) evaluated the congruence in estimates and precision of long‐ and short‐term Ne, Nem and m from six methods; (ii) explored the effects of metapopulation structure on Ne estimation in one system with spatiotemporally linked subpopulations, using three approaches; and (iii) determined to what degree interpopulation gene flow was asymmetric over time. We found that long‐term Ne estimates exceeded short‐term Ne within populations by 2–10 times; the two were correlated in the system with temporally stable structure (Atlantic salmon, Salmo salar) but not in the highly dynamic system (brown trout, Salmo trutta). Four temporal methods yielded short‐term Ne estimates within populations that were strongly correlated, and these were higher but more variable within salmon populations than within trout populations. In trout populations, however, these short‐term Ne estimates were always lower when assuming gene flow than when assuming no gene flow. Linkage disequilibrium data generally yielded short‐term Ne estimates of the same magnitude as temporal methods in both systems, but the two were uncorrelated. Correlations between long‐ and short‐term geneflow estimates were inconsistent between methods, and their relative size varied up to eightfold within systems. While asymmetries in gene flow were common in both systems (58–63% of population‐pair comparisons), they were only temporally stable in direction within certain salmon population pairs, suggesting that gene flow between particular populations is often intermittent and/or variable. Exploratory metapopulation Ne analyses in trout demonstrated both the importance of spatial scale in estimating Ne and the role of gene flow in maintaining genetic variability within subpopulations. Collectively, our results illustrate the utility of comparatively applying Ne, Nem and m to (i) tease apart processes implicated in population structure, (ii) assess the degree of continuity in patterns of connectivity between population pairs and (iii) gauge the relative performance of different approaches, such as the influence of population subdivision and gene flow on Ne estimation. They further reiterate the importance of temporal sampling replication in population genetics, the value of interpreting Neor m in light of species biology, and the need to address long‐standing assumptions of current Ne, Nem or m models more explicitly in future research.
In vitro transposition of ISY100, a bacterial insertion sequence belonging to the Tc1/mariner family
Authors: Feng Xiaofeng , Colloms Sean D. 
Published: August 2007

SummaryThe Synechocystis sp. PCC6803 insertion sequence ISY100 (ISTcSa) belongs to the Tc1/mariner/IS630 family of transposable elements. ISY100 transposase was purified and shown to promote transposition in vitro. Transposase binds specifically to ISY100 terminal inverted repeat sequences via an N‐terminal DNA‐binding domain containing two helix–turn–helix motifs. Transposase is the only protein required for excision and integration of ISY100. Transposase made double‐strand breaks on a supercoiled DNA molecule containing a mini‐ISY100 transposon, cleaving exactly at the transposon 3′ ends and two nucleotides inside the 5′ ends. Cleavage of short linear substrates containing a single transposon end was less precise. Transposase also catalysed strand transfer, covalently joining the transposon 3′ end to the target DNA. When a donor plasmid carrying a mini‐ISY100 was incubated with a target plasmid and transposase, the most common products were insertions of one transposon end into the target DNA, but insertions of both ends at a single target site could be recovered after transformation into Escherichia coli. Insertions were almost exclusively into TA dinucleotides, and the target TA was duplicated on insertion. Our results demonstrate that there are no fundamental differences between the transposition mechanisms of IS630 family elements in bacteria and Tc1/mariner elements in higher eukaryotes.
The staphylococcal respiratory response regulator SrrAB induces ica gene transcription and polysaccharide intercellular adhesin expression, protecting Staphylococcus aureus from neutrophil killing under anaerobic growth conditions
Authors: Ulrich Martina , Bastian Mike , Cramton Sarah E. , Ziegler Katrin , Pragman Alexa A. , Bragonzi Alessandra , Memmi Guido , Wolz Christiane , Schlievert Patrick M. , Cheung Ambrose , Döring Gerd 
Published: August 2007

SummaryIn anaerobic environments, Staphylococcus aureus increases the transcription of the intercellular adhesin (ica) cluster, leading to increased polysaccharide intercellular adhesin (PIA) production. The regulatory mechanisms involved in this phenotypic change are mostly unknown. Here we show that the staphylococcal respiratory response regulator, SrrAB, significantly increases icaA transcription under anaerobic growth in S. aureus. Phosphorylated SrrA preferentially bound to a 100 bp DNA sequence located upstream of ica, and dot blot assays revealed little or no PIA expression in S. aureus srrAB deletion‐replacement mutants of strains Sa113 and SH1000, grown anaerobically. The biological relevance of SrrAB for S. aureus was assessed in a phagocytosis assay employing human neutrophils. Sixty‐eight per cent of PIA producing wild‐type cells, but only 19% of srrAB mutant cells survived under anaerobic conditions, suggesting that PIA protected S. aureus against non‐oxidative killing mechanisms of the neutrophils. No protection was observed when S. aureus or S. epidermidis strains, producing PIA also under aerobic conditions, were subjected to phagocytosis under aerobic conditions. These results demonstrate that SrrAB is a major activator of ica expression and PIA production in anaerobic environments, where it contributes to the protection of S. aureus against non‐oxidative defence mechanisms.
Root growth dynamics of Nicotiana attenuata seedlings are affected by simulated herbivore attack
Authors: HUMMEL GRÉGOIRE M. , NAUMANN MARIA , SCHURR ULRICH , WALTER ACHIM 
Published: August 2007

ABSTRACTMany studies demonstrate resource‐based trade‐offs between growth and defence on a large timescale. Yet, the short‐term dynamics of this growth reaction are still completely unclear, making it difficult to explain growth‐defence trade‐offs mechanistically. In this study, image‐based non‐destructive methods were used to quantify root growth reactions happening within hours following simulated herbivore attack. The induction of wound reactions in Nicotiana attenuata in the seedling stage led to transiently decreased root growth rates. Application of the oral secretion of the specialist herbivore Manduca sexta to the leaves led to a transient decrease in root growth that was more pronounced than if a mere mechanical wounding was imposed. Root growth reduction was more pronounced than leaf growth reduction. When fatty acid–amino acid conjugates (FACs) were applied to wounds, root growth reduction occurred in the same intensity as when oral secretion was applied. Timing of the transient growth reduction coincided with endogenous bursts of jasmonate (JA) and ethylene emissions reported in literature. Simulation of a wound response by applying methyl jasmonate (MeJA) led to more prolonged negative effects on root growth. Increased nicotine concentrations, trichome lengths and densities were observed within 72 h in seedlings that were treated with MeJA or that were mechanically wounded. Overall, these reactions indicate that even in a very early developmental stage, the diversion of plant metabolism from primary (growth‐sustaining) to secondary (defence‐related) metabolism can cause profound alterations of plant growth performance.
TERE; a novel cis‐element responsible for a coordinated expression of genes related to programmed cell death and secondary wall formation during differentiation of tracheary elements
Authors: Pyo Hyunjin , Demura Taku , Fukuda Hiroo 
Published: August 2007

SummaryThe differentiation of water‐conducting tracheary elements (TEs) is the result of the orchestrated construction of secondary wall structure, including lignification, and programmed cell death (PCD), including cellular autolysis. To understand the orchestrated regulation of differentiation of TEs, we investigated the regulatory mechanism of gene expression directing TE differentiation. Detailed loss‐of‐function and gain‐of‐function analyses of the ZCP4 (Zinniacysteine protease 4) promoter, which confers TE‐specific expression, demonstrated that a novel 11‐bp cis‐element is necessary and sufficient for the immature TE‐specific promoter activity. The 11‐bp cis‐element‐like sequences were found in promoters of many Arabidopsis TE differentiation‐related genes. A gain‐of‐function analysis with similar putative cis‐elements from secondary wall formation or modification‐related genes as well as PCD‐related genes indicated that the cis‐elements are also sufficient for TE‐specific expression of genes. These results demonstrate that a common sequence, designated as the tracheary‐element‐regulating cis‐element, confers TE‐specific expression to both genes related to secondary wall formation or modification and PCD.
Maximum Likelihood Estimation in Semiparametric Regression Models with Censored Data
Authors: Zeng D. , Lin D. Y. 
Published: August 2007

SummarySemiparametric regression models play a central role in formulating the effects of covariates on potentially censored failure times and in the joint modelling of incomplete repeated measures and failure times in longitudinal studies. The presence of infinite dimensional parameters poses considerable theoretical and computational challenges in the statistical analysis of such models. We present several classes of semiparametric regression models, which extend the existing models in important directions. We construct appropriate likelihood functions involving both finite dimensional and infinite dimensional parameters. The maximum likelihood estimators are consistent and asymptotically normal with efficient variances. We develop simple and stable numerical techniques to implement the corresponding inference procedures. Extensive simulation experiments demonstrate that the inferential and computational methods proposed perform well in practical settings. Applications to three medical studies yield important new insights. We conclude that there is no reason, theoretical or numerical, not to use maximum likelihood estimation for semiparametric regression models. We discuss several areas that need further research.
HLA Dr‐Dq haplotypes and the TNFA‐308 polymorphism: associations with asthma and allergy
Authors: Munthe‐Kaas M. C. , Carlsen K. L. , Carlsen K. H. , Egeland T. , Håland G. , Devulapalli C. S. , Akselsen H. , Undlien D. 
Published: August 2007

Background:  The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor α gene (TNFA) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits.Methods:  The DRB1–DQB1 alleles and TNFA‐308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non‐allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses.Results:  Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA‐308A allele [Odds ratio (OR) 1.7 (1.3–2.3)] and DRB1*03 allele [OR 1.6(1–2.6)], but extended DRB1*03‐TNFA‐308 haplotype analysis suggested that the DRB1–DQB1 association was secondary to linkage disequilibrium with the TNFA‐308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1*0603‐DRB1*13 [OR 2.3 (1.4–4.0)] and mugwort sensitization with DQB1*0609‐DRB1*13 [OR 7.1 (1.9–27.0)] and DQB1*0501‐DRB1*01 [OR 2.0 (1.0–4.0)].Conclusions:  Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1*0603‐DRB1*13 and birch allergy is identified.
Bronchial hyperresponsiveness in young children with allergic rhinitis and its risk factors
Authors: Choi S. H. , Yoo Y. , Yu J. , Rhee C.‐S. , Min Y.‐G. , Koh Y. Y. 
Published: August 2007

Background:  Subjects with allergic rhinitis but no clinical evidence of asthma have greater bronchial hyperresponsiveness (BHR), and several factors have been implicated as its determinants. However, studies in young children are lacking. The aims of this study were to evaluate the prevalence of BHR in young children with allergic rhinitis and to investigate its risk factors.Methods:  Methacholine bronchial challenges were performed in 4‐ to 6‐year‐old nonasthmatic children with allergic rhinitis (n = 83) and in healthy nonatopic controls (n = 32), using a modified auscultation method. The end‐point was defined as the appearance of wheezing and/or oxygen desaturation. Subjects were considered to have BHR when they had end‐point concentrations of methacholine ≤8 mg/mL. Clinical and laboratory data in allergic rhinitis patients and a history of allergic diseases in their parents were collected.Results:  BHR was observed in 27 subjects with allergic rhinitis (32.5%) and three controls (9.4%). Among subjects with allergic rhinitis, serum total IgE, the number and pattern of skin‐prick test responses, blood eosinophil markers, and parental history of allergic rhinitis and atopic dermatitis were not different between the BHR(+) and BHR(−) groups, whereas the persistent type of rhinitis and parental history of asthma were more frequent in the BHR(+) group than in the BHR(−) group. These associations remained significant in a multivariable logistic regression.Conclusions:  Young children with allergic rhinitis alone showed an increased prevalence of BHR. Both persistent type of rhinitis and parental history of asthma were significant and independent risk factors for BHR in these children.
Nasal epithelial cells express IL‐10 at levels that negatively correlate with clinical symptoms in patients with house dust mite allergy
Authors: Muller B. , De Groot E. J. J. , Kortekaas I. J. M. , Fokkens W. J. , Van Drunen C. M. 
Published: August 2007

Background:  Despite constant exposure to micro‐organisms and other immunogenic environmental factors, relatively very few immunological responses are initiated in the nasal mucosa. Although several mechanisms could play a role in maintaining this immune suppressive milieu, none of them have been validated. Previous data from our group suggested that locally produced interleukin (IL)‐10 could be involved in maintaining local homeostasis.Methods:  To investigate the role of epithelial IL‐10 expression in the manifestation of allergic symptoms, we used immunohistochemistry to study the expression of IL‐10 in the nasal epithelium of healthy individuals and house dust mite allergic patients. In the allergic patients, we determined potential correlations of epithelial expression with allergic symptoms, both at baseline and after allergen provocation.Results:  IL‐10 is expressed in the basal and differentiated epithelial cells of both healthy individuals and allergic rhinitis patients. In the allergic individuals, there is a strong negative correlation at baseline between the epithelial expression level of IL‐10 and rhinorrhoea and sneezing, but not between that expression level and nasal blockage or peak nasal inspiratory flow (PNIF). This correlation disappears with steroid treatment or after allergen provocation, although the expression at baseline seems to predict PNIF scores after provocation.Conclusions:  Our data not only reveals IL‐10 expression by human nasal epithelial cells, but also suggests that nasal epithelial IL‐10 regulates allergic symptoms. Targeting the regulation mechanisms affecting IL‐10 or targeting the regulation mechanism affected by IL‐10 could constitute new options for the treatment of allergic disease.
Effects of pollen and nasal glucocorticoid on FOXP3+, GATA‐3+ and T‐bet+ cells in allergic rhinitis
Authors: Malmhäll C. , Bossios A. , Pullerits T. , Lötvall J. 
Published: August 2007

Background:  T‐regulatory cells (Treg) affect the balance of TH2 and TH1 cells. Treg, TH2 and TH1 cells are regulated by the FOXP3, GATA‐3 and T‐bet transcription factors respectively. Our aim was to determine the number of FOXP3+, GATA‐3+ and T‐bet+ cells in nasal mucosa in symptom‐free allergic rhinitis (AR) patients vs healthy controls, as well as the effects of natural pollen exposure and concomitant nasal glucocorticoid treatment on these cells.Methods:  Nasal biopsies were taken from healthy controls and patients with grass‐pollen AR preseason. The AR patients were randomized to receive treatment with either fluticasone propionate (FP) or a placebo, and additional biopsies were taken during the pollen season. FOXP3+, GATA‐3+ and T‐bet+ cells in nasal mucosa were quantified by immunohistochemistry.Results:  The number of FOXP3+ and GATA‐3+ cells, but not T‐bet+ cells, was significantly higher in AR patients vs controls preseason. The number of FOXP3+ cells remained unchanged in the former group after the pollen season but decreased significantly in the nasal mucosa as a result of FP treatment. The pollen season substantially increased the number of GATA‐3+ cells, which was inhibited by FP. The number of T‐bet+ cells was not affected by pollen or FP.Conclusion:  These data suggest that nasal glucocorticoids attenuate the allergic inflammation partly by reducing the number of TH2 cells, but not by means of local upregulation of Treg cells. The local relationship between TH1 and TH2 cells as well as between Treg and TH2 is maintained by nasal glucocorticoid treatment.
Today’s allergic rhinitis patients are different: new factors that may play a role
Authors: Mösges R. , Klimek L. 
Published: August 2007

Most of today’s patients suffering from allergic rhinitis (AR) are sensitized to more than one trigger and suffer from persistent and moderate/severe symptoms, which severely impair their quality of life (QOL). The objective of this article was to review the data on the effect of increased air pollution, changes in indoor environment/lifestyle/affluence, exposure to new allergens and psychologically stressful lifestyles, as also to explore their potential in the development of this more ‘aggressive’ form of disease.Increased fossil fuel‐generated air pollution may increase the risk of allergic sensitization, airway responsiveness to allergens, and allergenicity and the bioavailability of airborne allergens. Changes in indoor environment/lifestyle/affluence appear to have led to more time being spent indoors and resulted in perennial exposure to indoor allergens, changes in sensitization patterns, and polysensitization to a variety of novel cross‐reacting exotic food and pet allergens. Although evidence suggests an association between psychological stress and increased risk for atopy and allergic disease, further studies are required to demonstrate this unequivocally.The more persistent and moderate/severe nature of the disease suggests a need for modification of current treatment strategies and advocacy of the use from the outset of agents, which are both efficacious and safe in managing severe and persistent AR symptoms and in improving the QOL of affected individuals.
Assessment of combined symptom and medication scores for rhinoconjunctivitis immunotherapy clinical trials
Authors: Clark J. , Schall R. 
Published: August 2007

Background:  In randomized, double‐blind, placebo‐controlled clinical trials the efficacy of immunotherapy for allergic rhinoconjunctivitis is evaluated using the Average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with lower ARTSS relative to placebo. For ethical reasons patients are provided with registered rescue medication, which may alleviate symptoms and thus reduce symptom scores. This effect biases the mean difference in ARTSS between effective treatment and placebo towards zero. Therefore, when rescue medication is taken by a patient, the ARTSS needs to be adjusted appropriately.Methods:  We considered five outcome measures: ARTSS, Average Rescue Medication Score (ARMS), and three combined symptom and RMSs. To assess the different outcome measures regarding their power to discriminate between effective treatment and placebo, we calculated their effect size when applied to data from a clinical trial of immunotherapy for allergic rhinoconjunctivitis.Results:  Of the five outcome measures considered, the average of the ARTSS and ARMS was associated with the largest effect size, and thus with the highest power to show treatment efficacy. Discriminant and multivariate analyses suggest that this average is approximately optimal among all weighted sums of ARTSS and ARMS.Conclusion:  Our findings support recommendations made in a World Allergy Organisation document on methodological aspects of immunotherapy trials. The average of the ARTSS and ARMS should be considered as a primary efficacy variable in clinical trials of immunotherapy for allergic rhinoconjunctivitis.
Relationship between ARIA classification and drug treatment in allergic rhinitis and asthma
Authors: Antonicelli L. , Micucci C. , Voltolini S. , Senna G. E. , Di Blasi P. , Visonà G. , De Marco R. , Bonifazi F. 
Published: August 2007

Introduction:  The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines provide a stepwise treatment to rhinitis, which classifies the disease according to its duration and severity.Objectives:  The aim of the study was to verify whether these variables influence drug prescriptions for rhinitis and asthma.Methods:  A multi‐centre cross‐sectional pharmaco‐epidemiological survey was carried out on 1610 allergic rhinitis patients and the relationship between the clinical features of rhinitis and drug therapy for rhinitis and asthma was evaluated.Results:  A total of 1321 adult patients were enrolled. Mild intermittent rhinitis was diagnosed in 7.7%of the patients, moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent in 63.6%. A high level of rhinitis‐asthma comorbidity (616/1321 = 46.6%) was found. The majority of patients [1060 (80.24%)] were treated. Significant associations between the severity of rhinitis and the presence of therapy (P = 0.008), the use of oral antihistamines (P < 0.001), topical nasal steroids (P = 0.020) and systemic steroids (P = 0.005) were found. A weak association was found between the features of rhinitis and the therapy for asthma, and vice versa the comorbidity with asthma increases the prescription of inhalant (P < 0.001) and oral steroids (P = 0.015) to treat rhinitis.Conclusion:  The severity of rhinitis influences patient request for rhinitis therapy and the type of medication more than the duration. These features of rhinitis seem to poorly influence asthma therapy. As the ARIA classification is able to reveal a relevant impairment notwithstanding therapy, its role in treated patients merits further study.