bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrolytic cleavage ofN6-substituted adenine derivatives by eukaryotic adenine and adenosine deaminases
Authors: PospíŠilová Hana , Šebela Marek , Novák Ondřej , Frébort Ivo 
Published: August 2008

Homogeneous adenine deaminases (EC 3.5.4.2) from the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and a putative ADA (adenosine deaminase; EC 3.5.4.4) from Arabidopsis thaliana were obtained for the first time as purified recombinant proteins by molecular cloning of the corresponding genes and their overexpression in Escherichia coli. The enzymes showed comparable molecular properties with well-known mammalian ADAs, but exhibited much lower kcat values. Adenine was the most favoured substrate for the yeast enzymes, whereas the plant enzyme showed only very low activities with either adenine, adenosine, AMP or ATP. Interestingly, the yeast enzymes also hydrolysed N6-substituted adenines from cytokinins, a group of plant hormones, cleaving them to inosine and the corresponding side chain amine. The hydrolytic cleavage of synthetic cytokinin 2,6-di-substituted analogues that are used in cancer therapy, such as olomoucine, roscovitine and bohemine, was subsequently shown for a reference sample of human ADA1. ADA1, however, showed a different reaction mechanism to that of the yeast enzymes, hydrolysing the compounds to an adenine derivative and a side chain alcohol. The reaction products were identified using reference compounds on HPLC coupled to UV and Q-TOF (quadrupole–time-of-flight) detectors.The ADA1 activity may constitute the debenzylation metabolic route already described for bohemine and, as a consequence, it may compromise the physiological or therapeutic effects of exogenously applied cytokinin derivatives.
BLogo: a tool for visualization of bias in biological sequences
Authors: Li Wencheng , Yang Bo , Liang Shaoguang , Wang Yonghua , Whiteley Chris , Cao Yicheng , Wang Xiaoning 
Published: August 2008

Abstract
Summary: Blogo is a web-based tool that detects and displays statistically significant position-specific sequence bias with reduced background noise. The over-represented and under-represented symbols in a particular position are shown above and below the zero line. When the sequences are in open reading frames, the background frequency of nucleotides could be calculated separately for the three positions of a codon, thus greatly reducing the background noise. The χ2-test or Fisher's exact test is used to evaluate the statistical significance of every symbol in every position and only those that are significant are highlighted in the resulting logo. The perl source code of the program is freely available and can be run locally.
Availability: http://acephpx.cropdb.org/blogo/, http://www.bioinformatics.org/blogo/
Contact: lwcbio@yahoo.com.cn; xnwang@21cn.net
Supplementary information: Supplementary data are available atBioinformatics online.
Late Holocene dispersal and accumulation of terrigenous sediment on Poverty Shelf, New Zealand
Authors: Kettner A. J. , Gomez B. , Hutton E. W. H. , Syvitski J. P. M. 
Published: August 2008

ABSTRACTWe use coupled numerical models (HydroTrend and SedFlux) to investigate the dispersal and accumulation of sediment on Poverty Shelf, North Island, New Zealand, during the past 3 kyr. In this timeframe, we estimate that the Waipaoa River system delivered ∼10 Gt of sediment to Poverty Shelf,  5–10% of which was transported to the outer shelf and continental slope. The domain of the two‐dimensional model (SedFlux) is representative of a 30 km traverse across the shelf. Comparing the model output with seismic reflection data and a core obtained from the middle shelf shows that, without extensively modifying the governing equations or imposing unrealistic conditions on the model domain, it is possible to replicate the geometry, grain size and accumulation rate of the late Holocene mud deposit. The replicate depositional record responds to naturally and anthropogenically induced vegetation disturbance, as well as to storms forced by long‐period climatic events simulated entirely within the model domain. The model output also suggests that long‐term fluctuations in the amount and caliber of river sediment discharge, promoted by wholesale changes in the catchment environment, may be translated directly to the shelf depositional record, whereas short‐term fluctuations conditioned by event magnitude and frequency are not. Thus on Poverty Shelf, as well as in depocenters on other active continental margins which retain a much smaller proportion of the terrigeneous sediment delivered to them, flood‐generated event beds are not commonplace features in the high‐resolution sedimentary record. This is because the shelf sedimentary record is influenced more by the energy available to the coastal ocean which helps keep the sediment in suspension and facilitates its dispersal, than by basin hydrometeorology which determines the turbidity and velocity of the river plume.
Suppressive effects of nitric oxide‐releasing prednisolone NCX‐1015 on the allergic pleural eosinophil recruitment in rats
Authors: Oliveira M. S. S. , De O. Barreto E. , Zamuner S. , Pires A. L. A. , Ferreira T. P. T. , Cordeiro R. S. B. , Lagente V. , Martins M. A. , Wallace J. L. , E Silva P. M. R. 
Published: August 2008

SummaryBackground
The addition of a nitric oxide (NO)‐releasing moiety to prednisolone was shown to enhance the anti‐inflammatory activity of this glucocorticoid in some experimental conditions, but its effectiveness in the context of eosinophilic inflammation remains to be elucidated.Objective
This study compared the anti‐inflammatory effect of prednisolone to a NO‐releasing derivative of prednisolone, NCX‐1015, using a model of allergen‐evoked eosinophil recruitment in rats. The efficacy of a NO‐donor compound, DETA‐NONOate, was also assessed for comparison.Methods
Wistar rats were actively sensitized with Al(OH)3 plus ovalbumin and 14 days later challenged with antigen intrapleurally. Treatments were performed locally 1 h before challenge. Cysteinyl‐leucotrienes (Cys‐LT) and eotaxin were measured by ELISA.Results
Antigen challenge induced an eosinophil infiltration at 12 h, maximal at 24 h. It also caused an increase in the levels of Cys‐LTs in the pleural exudate and in the expression of 5‐lipoxygenase (5‐LO) in infiltrated leucocytes at 6 h, peaking at 12 h and persisting for at least 24 h. Treatment with equimolar doses of prednisolone and NCX‐1015 inhibited the late eosinophil infiltration, although the dose required to produce maximal inhibition was about one‐tenth that of prednisolone. Cys‐LT generation and 5‐LO expression were inhibited by NCX‐1015 but not by prednisolone. Treatment with prednisolone combined with the NO‐donor DETA‐NONOate led to a greater inhibition of the eosinophilia and Cys‐LT generation as compared with either drug alone. Administration of the steroid receptor antagonist RU 486, 1 h before prednisolone and NCX‐1015, abolished the inhibitory effect of the former, under conditions where it only partially affected the latter.Conclusions
Our findings indicate that NCX‐1015 provided a greater anti‐inflammatory effect than prednisolone on the allergic eosinophil recruitment in rats, suggesting that NO‐releasing steroids can be considered as a promising therapeutic approach to allergic diseases.
Effects of forest fire on headwater stream macroinvertebrate communities in eastern Washington, U.S.A.
Authors: MELLON CASSIE D. , WIPFLI MARK S. , LI JUDITH L. 
Published: August 2008

Summary1. Recent increases in fire frequency in North America have focused interest on potential effects on adjacent ecosystems, including streams. Headwaters could be particularly affected because of their high connectivity to riparian and downstream aquatic ecosystems through aquatic invertebrate drift and emergence.2. Headwater streams from replicated burned and control catchments were sampled in 2 years following an intense forest fire in northeastern Washington (U.S.A.). We compared differences in benthic, drift and emergent macroinvertebrate density, biomass and community composition between five burned and five unburned catchments (14–135 ha).3. There were significantly higher macroinvertebrate densities in burned than control sites for all sample types. Macroinvertebrate biomass was greater at burned sites only from emergence samples; in benthic and drift samples there was no significant difference between burn and control sites.4. For all sample types, diversity was lower in the burned catchments, and the macroinvertebrate community was dominated by chironomid midges.5. Compared to the effects of fire in less disturbed ecosystems, this study illustrated that forest fire in a managed forest may have greater effects on headwater macroinvertebrate communities, influencing prey flow to adjacent terrestrial and downstream aquatic habitats for at least the first 2 years post‐fire.
Critical evaluation of regulatory T cells in autoimmunity: are the most potent regulatory specificities being ignored?
Authors: Vandenbark Arthur A. , Offner Halina 
Published: August 2008

SummaryThe identification of CD4+ CD25+ Foxp3+ regulatory T (Treg) cells as natural regulators of immunity in the periphery and tissues has stimulated tremendous interest in developing therapeutic strategies for autoimmune diseases. In this review, the site of origin, antigen specificity, homing markers and cytokine profiles of Treg cells were evaluated in autoimmune colitis and type 1 diabetes, two examples in which Treg cells were effective as therapy. These studies were compared with studies of Treg cells in experimental autoimmune encephalomyelitis and multiple sclerosis, where successful therapy has not yet been achieved. Antigen‐specific Treg cells appear to have more potent activity than polyclonal Treg cells and therefore hold more promise as therapeutic agents. However, Treg cells specific for the pathogenic T effector cells themselves have largely been overlooked and deserve consideration in future studies.
Real time PCR detection of Piscirickettsia salmonis from formalin‐fixed paraffin‐embedded tissues
Authors: Karatas S , Mikalsen J , Steinum T M , Taksdal T , Bordevik M , Colquhoun D J 
Published: August 2008

Abstract Piscirickettsia salmonis is the causative agent of piscirickettsiosis, a transmissible disease of salmonid fish. Diagnosis of piscirickettsiosis has traditionally been based upon identification of typical pathological changes by histological investigation, with confirmation by immunohistochemistry on formalin‐fixed, paraffin‐embedded tissues. However, implementation of more rapid confirmatory techniques, preferably with higher levels of sensitivity and possibilities for quantification, is desirable. A real‐time polymerase chain reaction (PCR) assay was designed for specific detection of P. salmonis and tested on samples extracted from formalin‐fixed paraffin‐embedded material. Construction of a PCR‐target mimic allowed determination of detection limits, linearity of the real‐time PCR and quantitative detection of P. salmonis. The present study demonstrates the capability of the described real time PCR assay for detection of P. salmonis from paraffin‐embedded material with a high degree of sensitivity and specificity. Implementation of this assay constitutes an important development for a rapid and secure diagnosis of piscirickettsiosis.
The presence of multiple c‐type cytochromes at the surface of the methanotrophic bacterium Methylococcus capsulatus (Bath) is regulated by copper
Authors: Karlsen O. A. , Lillehaug J. R. , Jensen H. B. 
Published: August 2008

SummaryIdentification of surface proteins is essential to understand bacterial communication with its environment. Analysis of the surface‐associated proteins of Methylococcus capsulatus (Bath) revealed a highly dynamic structure responding closely to the availability of copper in the medium in the range from ∼0 to 10 μM. Several c‐type cytochromes, including three novel multihaem proteins, are present at the cellular surface, a feature that is otherwise a peculiarity of dissimilatory metal‐reducing bacteria. At low copper concentrations, the cytochrome c553o and the cytochrome c553o family protein, encoded by the MCA0421 and MCA0423 genes, respectively, are major constituents of the surfaceome and show a fine‐tuned copper‐dependent regulation of expression. Two novel members of the cytochrome c553o family were identified: MCA0338 was abundant between 5 and 10 μM copper, while MCA2259 was detected only in the surface fraction obtained from ∼0 μM copper cultures. The presence at the bacterial surface of several c‐type cytochromes, generally involved in energy transduction, indicates strongly that redox processes take place at the bacterial surface. Due to the unique role of copper in the biology of M. capsulatus (Bath), it appears that c‐type cytochromes have essential functions in copper homeostasis allowing the cells to adapt to varying copper exposure.
Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence
Authors: Beydoun Hind , Saftlas Audrey F. 
Published: August 2008

SummaryPrenatal maternal stress (PNMS) has been linked with adverse health outcomes in the offspring through experimental studies using animal models and epidemiological studies of human populations. The purpose of this review article is to establish a parallel between animal and human studies, while focusing on methodological issues and gaps in knowledge. The review examines the quality of recent evidence for prevailing PNMS theoretical models, namely the biopsychosocial model for adverse pregnancy outcomes and the fetal programming model for chronic diseases. The investigators used PubMed (2000–06) to identify recently published original articles in the English language literature. A total of 103 (60 human and 43 animal) studies were examined.Most human studies originated from developed countries, thus limiting generalisability to developing nations. Most animal studies were conducted on non‐primates, rendering extrapolation of findings to pregnant women less straightforward. PNMS definition and measurement were heterogeneous across studies examining similar research questions, thus precluding the conduct of meta‐analyses. In human studies, physical health outcomes were often restricted to birth complications while mental health outcomes included postnatal developmental disorders and psychiatric conditions in children, adolescents and adults. Diverse health outcomes were considered in animal studies, some being useful models for depression, schizophrenia or attention deficit hyperactivity disorder in human populations. The overall evidence is consistent with independent effects of PNMS on perinatal and postnatal outcomes. Intervention studies and large population‐based cohort studies combining repeated multi‐dimensional and standardised PNMS measurements with biomarkers of stress are needed to further understand PNMS aetiology and pathophysiology in human populations.
Birth prevalence of congenital hypothyroidism in Mexico
Authors: Rendón‐Macías Mario E. , Morales‐García Inés , Huerta‐Hernández Emilio , Silva‐Batalla Anabel , Villasís‐Keever Miguel A. 
Published: August 2008

SummaryThe Mexican Institute of Social Security (IMSS) provides care for more than 40% of the Mexican population. This report constitutes the first study of the incidence of congenital hypothyroidism (CH) in Mexican children. We performed a prospective study with a population base. CH screening began in 1997 with blood samples from the heel taken 72 h after birth; from 2000, the detection strategy was changed nationwide and blood samples were taken from the umbilical cord in all newborns for determination of thyroid‐stimulating hormone (TSH) concentration. We evaluated the annual coverage. TSH concentration was measured by chemoluminescence; TSH values ≥30 µIU/mL in umbilical cord blood and 15 µIU/mL in capillary blood were considered positive cases and were confirmed through hormonal studies. The incidence and 95% confidence intervals [95% CI] were calculated.We found that coverage within the IMSS population was 53% from 1997 to 2000 and had increased to 95% by 2001. A total of 2 777 292 children from 2 975 157 births (93%) were studied between 2000 and 2004. Of these, 4050 had a high TSH concentration leading to suspicion of CH; CH was confirmed in 1286 (32%). The resulting incidence was 4.3/10 000 livebirths [95% CI 3.6, 5.1]. With the results obtained, we conclude that the IMSS strategy of CH screening at birth ensured 95% coverage of children in the system. The birth prevalence of CH reported is among the highest in the world.
To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection
Authors: Schisterman Enrique F. , Vexler Albert 
Published: August 2008

SummaryPooling of biological specimens has been utilised as a cost‐efficient sampling strategy, but cost is not the unique limiting factor in biomarker development and evaluation. We examine the effect of different sampling strategies of biospecimens for exposure assessment that cannot be detected below a detection threshold (DT). The paper compares use of pooled samples to a randomly selected sample from a cohort in order to evaluate the efficiency of parameter estimates.The proposed approach shows that a pooling design is more efficient than a random sample strategy under certain circumstances. Moreover, because pooling minimises the amount of information lost below the DT, the use of pooled data is preferable (in a context of a parametric estimation) to using all available individual measurements, for certain values of the DT. We propose a combined design, which applies pooled and unpooled biospecimens, in order to capture the strengths of the different sampling strategies and overcome instrument limitations (i.e. DT). Several Monte Carlo simulations and an example based on actual biomarker data illustrate the results of the article.
Antibody responses induced by Trichobilharzia regenti antigens in murine and human hosts exhibiting cercarial dermatitis
Authors: LICHTENBERGOVÁ L. , KOLBEKOVÁ P. , KOUŘILOVÁ P. , KAŠNÝ M. , MIKEŠ L. , HAAS H. , SCHRAMM G. , HORÁK P. , KOLÁŘOVÁ L. , MOUNTFORD A. P. 
Published: August 2008

SUMMARY Cercariae of bird schistosomes (genus Trichobilharzia) are able to penetrate the skin of mammals (noncompatible hosts), including humans, and cause a Th2‐associated inflammatory cutaneous reaction termed cercarial dermatitis. The present study measured the antibody reactivity and antigen specificity of sera obtained after experimental infection of mice and natural infection of humans. Sera from mice re‐infected with T. regenti showed a bias towards the development of antigen‐specific IgM and IgG1 antibodies and elevated levels of total serum IgE, indicative of a Th2 polarized immune response. We also demonstrate that cercariae are a source of antigens triggering IL‐4 release from basophils collected from healthy human volunteers. Analysis of sera from patients with a history of cercarial dermatitis revealed elevated levels of cercarial‐specific IgG, particularly for samples collected from adults (> 14 years old) comparedwith children (8–14 years old), although elevated levels of antigen‐specific IgE were not detected. In terms of antigen recognition, IgG and IgE antibodies in the sera of both mice and humans preferentially bound an antigen of 34 kDa. The 34 kDa molecule was present in both homogenate of cercariae, as well as cercarial excretory/secretory products, and we speculate it may represent a major immunogen initiating the Th2‐immune response associated with cercarial dermatitis.
Downregulation of CXCR6 and CXCR3 in Lymphocytes from Birch‐allergic Patients
Authors: Casas R. , Lindau C. , Zetterström O. , Duchén K. 
Published: August 2008

AbstractPreferential expression of chemokine receptors on Th1 or Th2 T‐helper cells has mostly been studied in cell lines generated in vitro or in animal models; however, results are less well characterized in humans. We determined T‐cell responses through chemokine receptor expression on lymphocytes, and cytokine secretion in plasma from birch‐allergic and healthy subjects. The expression of CCR2, CCR3, CCR4, CCR5, CCR7, CXCR3, CXCR4, CXCR6, IL‐12 and IL‐18R receptors was studied on CD4+ and CD8+ cells from birch‐allergic (n = 14) and healthy (n = 14) subjects by flow cytometry. The concentration of IL‐4, IL‐5, IL‐10, IL‐12, IFN‐γ and TNF‐α cytokines was measured in plasma from the same individuals using a cytometric bead array human cytokines kit. The similar expression of CCR4 in T cells from atopic and healthy individuals argues against the use of the receptor as an in vivo marker of Th2 immune responses. Reduced percentages of CD4+ cells expressing IL‐18R, CXCR6 and CXCR3 were found in the same group of samples. TNF‐α, IFN‐γ, IL‐10, IL‐5, IL‐4 and IL‐12 cytokines were elevated in samples from allergic individuals. Reduced expression of Th1‐associated chemokine receptors together with higher levels of Th1, Th2 and anti‐inflammatory cytokines in samples from allergic patients indicate that immune responses in peripheral blood in atopic diseases are complex and cannot be simplified to the Th1/Th2 paradigm. Not only the clinical picture of atopic diseases but also the clinical state at different time points of the disease might influence the results of studies including immunological markers associated with Th1‐ or Th2‐type immune responses.
T‐cell activation during exacerbations: a longitudinal study in refractory asthma
Authors: Mamessier E. , Nieves A. , Lorec A.‐M. , Dupuy P. , Pinot D. , Pinet C. , Vervloet D. , Magnan A. 
Published: August 2008

Background:  Asthma exacerbations represent the main source of costs and morbidity in asthma care, and drugs specifically designed to prevent exacerbations are needed. A prerequisite is to dispose of a precise knowledge of inflammatory events leading to exacerbations.Objective:  To study T‐cell activation during exacerbations from severe refractory asthmatics.Methods:  Proportions of blood T‐cell interleukin (IL)‐13, interferon‐γ, IL‐4, IL‐5, IL‐10 production and of CD4+CD25+highCD62L+CD45RO+ [T regulatory (Treg)] cells were determined by flow cytometry. Blood cytokine mRNA was studied by reverse transcription‐polymerase chain reaction and the respective protein levels were determined by cytokine beads array. Depletion of Treg cells was performed to study their activation. T‐cell cytokines were detected in parallel in induced sputum.Results:  At baseline, T helper 2 (Th2) cells were increased in asthmatics, whereas T helper 1 (Th1) and Treg T cells were decreased. T helper 2 cells increased before exacerbations, followed by Th1 cells, in blood and induced sputum, albeit Treg cells decreased in parallel with IL‐10‐producing T cells. Concordant results were found at the mRNA level. The suppressive activity of Treg cells was impaired during exacerbations compared to baseline.Conclusions:  New insights are given into pathophysiology of asthma exacerbations: Although at baseline T‐cell activation is Th2‐biased, a mixed Th1/Th2 activation occurs during exacerbations. The Treg cell deficiency found at baseline in SRA increases during exacerbations.