bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Novel Glycosyltransferases Required for Assembly of the
Pasteurella multocida
A:1 Lipopolysaccharide and Their Involvement in Virulence
Authors: Boyce John D. , Harper Marina , St. Michael Frank , John Marietta , Aubry Annie , Parnas Henrietta , Logan Susan M. , Wilkie Ian W. , Ford Mark , Cox Andrew D. , Adler Ben 
Published: January 2009

ABSTRACT

We previously determined the structure of the
Pasteurella multocida
Heddleston type 1 lipopolysaccharide (LPS) molecule and characterized some of the transferases essential for LPS biosynthesis. We also showed that
P. multocida
strains expressing truncated LPS display reduced virulence. Here, we have identified all of the remaining glycosyltransferases required for synthesis of the oligosaccharide extension of the
P. multocida
Heddleston type 1 LPS, including a novel α-1,6 glucosyltransferase, a β-1,4 glucosyltransferase, a putative bifunctional galactosyltransferase, and two heptosyltransferases. In addition, we identified a novel oligosaccharide extension expressed only in a heptosyltransferase (
hptE
) mutant background. All of the analyzed mutants expressing LPS with a truncated main oligosaccharide extension displayed reduced virulence, but those expressing LPS with an intact heptose side chain were able to persist for long periods in muscle tissue. The
hptC
mutant, which expressed LPS with the shortest oligosaccharide extension and no heptose side chain, was unable to persist on the muscle or cause any disease. Furthermore, all of the mutants displayed increased sensitivity to the chicken antimicrobial peptide fowlicidin 1, with mutants expressing highly truncated LPS being the most sensitive.
Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis Due to
Leishmania guyanensis
Authors: Bourreau E. , Ronet C. , Darcissac E. , Lise M. C. , Sainte Marie D. , Clity E. , Tacchini-Cottier F. , Couppie P. , Launois P. 
Published: January 2009

ABSTRACT

The levels of regulatory T cells (Treg cells), analyzed by Foxp3 mRNA expression, were determined in lesions from patients with acute cutaneous leishmaniasis (ACL) and chronic cutaneous leishmaniasis (CCL). We demonstrated that Treg cells preferentially accumulate in lesions from ACL patients during the early phase of infection (lesion duration of less than 1 month). In addition, levels of Foxp3 mRNA transcripts were significantly higher in specimens from patients with CCL than in those from patients with ACL, suggesting a critical role of intralesional Treg cells in CCL. Intralesional Treg cells from both ACL and CCL patients were shown to have suppressive functions in vitro, since they inhibited the gamma interferon (IFN-γ) produced by CD4
+
CD25
−
T cells purified from peripheral blood mononuclear cells from the same patient in response to
Leishmania guyanensis
stimulation. Intralesional 2,3-indoleamine dioxygenase (IDO) mRNA expression was associated with that of Foxp3, suggesting a role for IDO in the suppressive activity of intralesional Treg cells. In addition, a role, albeit minor, of interleukin-10 (IL-10) was also demonstrated, since neutralization of IL-10 produced by intralesional T cells increased IFN-γ production by effector cells in an in vitro suppressive assay. These results confirm the role of intralesional Treg cells in the immunopathogenesis of human
Leishmania
infection, particularly in CCL patients.
Overexpression of MazF
Sa
in
Staphylococcus aureus
Induces Bacteriostasis by Selectively Targeting mRNAs for Cleavage
Authors: Fu Zhibiao , Tamber Sandeep , Memmi Guido , Donegan Niles P. , Cheung Ambrose L. 
Published: January 2009

ABSTRACT

The role of chromosomally encoded toxin-antitoxin (TA) loci in bacterial physiology has been under debate, with the toxin proposed as either an inducer of bacteriostasis or a mediator of programmed cell death (PCD). We report here that ectopic expression of MazF
Sa
, a toxin of the TA module from
Staphylococcus aureus
, led to a rapid decrease in CFU counts but most cells remained viable as determined by differential Syto 9 and propidium iodide staining after MazF
Sa
induction. This finding suggested that the toxin MazF
Sa
induced cell stasis rather than cell death. We also showed that MazF
Sa
selectively cleaves cellular mRNAs in vivo, avoiding “important” transcripts such as
recA
,
gyrB
, and
sarA
mRNAs in MazF
Sa
-induced cells, while these three mRNAs can be cleaved in vitro. The results of Northwestern blotting showed that both
sarA
and
recA
mRNAs bind strongly to a putative RNA-binding protein. These data suggest that
S. aureus
likely undergoes stasis by protecting selective mRNA with RNA-binding proteins upon the expression of MazF
Sa
in vivo.
Maturation of the Translation Inhibitor Microcin C
Authors: Metlitskaya Anastasia , Kazakov Teymur , Vondenhoff Gaston H. , Novikova Maria , Shashkov Alexander , Zatsepin Timofei , Semenova Ekaterina , Zaitseva Natalia , Ramensky Vasily , Van Aerschot Arthur , Severinov Konstantin 
Published: January 2009

ABSTRACT

Microcin C (McC), an inhibitor of the growth of enteric bacteria, consists of a heptapeptide with a modified AMP residue attached to the backbone of the C-terminal aspartate through an
N
-acyl phosphamidate bond. Here we identify maturation intermediates produced by cells lacking individual
mcc
McC biosynthesis genes. We show that the products of the
mccD
and
mccE
genes are required for attachment of a 3-aminopropyl group to the phosphate of McC and that this group increases the potency of inhibition of the McC target, aspartyl-tRNA synthetase.
Physical and ecological response to disturbance by gravel mining in a large alluvial river
Authors: Rempel Laura L. , Church Michael 
Published: January 2009

The role of sediment transport during high flows for restoring fish habitat was demonstrated following an experimental gravel removal from Fraser River, British Columbia, Canada. Dry bar scalping 69 000 m3 of river sediment left a topographically simple removal area with a loose surface of gravel and sand. Two subsequent, below-average floods yielded no gravel replenishment but restored substrate grain size and some topographical complexity at the habitat scale. A third, above-average flood replenished 31% of the removal volume. High-elevation bar area, which provides fish habitat at high flows, remained 25% smaller after the three floods. Effects of mining on the fish community could not be confirmed. Benthic invertebrates recolonized the removal site immediately after mining, and differences in community composition compared with three reference sites disappeared during the first flood. Results suggest that physical changes due to this mining operation fell within the range to which local aquatic populations are accustomed during flooding, because the ecological response was modest and short-lived. Despite an extensive sampling program, inherent variability in the biological data reduced statistical power to detect an effect. Monitoring programs to support adaptive management of river fisheries will require substantial investment and planning to yield definitive results.
Genetic variability in reaction norms between farmed and wild backcrosses of Atlantic salmon (Salmo salar)
Authors: Darwish Tamara L. , Hutchings Jeffrey A. 
Published: January 2009

Adaptive responses to environmental heterogeneity may vary among populations. Genetic variability in reaction norms might account for population differences in the ability to respond to environmental change and may reflect local adaptation. Reaction norms for early life history traits were compared among three population crosses of Atlantic salmon ( Salmo salar ). Two comprised second-generation backcrosses introgressed with either farmed or wild genes; the third comprised individuals from a second-generation, pure wild cross. Using a common-garden experimental protocol, each cross was exposed to three temperature regimes. Plasticity in embryonic development, growth, survival, and body size was measured from fertilization up to 24 weeks of exogenous feeding. Reaction norms differed markedly among crosses, irrespective of whether individuals interbred with those whose genes originated from another wild population or from a cultured population. We find that introgression involving individuals with comparatively few genetic differences can change reaction norms. If plasticity represents an adaptive response to local environments, then changes to reaction norms resulting from interbreeding between populations are unlikely to have a beneficial effect on fitness.
Spatial and temporal impact of pingers on porpoises
Authors: Carlström Julia , Berggren Per , Tregenza Nick J.C. 
Published: January 2009

Bycatches are considered the most serious threat to harbour porpoises ( Phocoena phocoena ) and other small cetaceans worldwide. Pingers are used to reduce bycatch levels, but may also deter porpoises from critical habitats. We investigated the spatial and temporal responses of porpoises to simulated bottom-set nets equipped with periodically operating Dukane NetMark 1000 pingers. Echolocation rates were monitored by porpoise click train detectors (PODs) placed at and around the nets, and a shore-based observation team recorded surfacing positions and movements. Pinger sound significantly reduced the median echolocation encounter rate by 50%–100% at PODs placed up to 500 m and reduced the sighting rate up to 375 m from the simulated net. The average distance of approach increased by 300 m. When pingers were silent after being active for 24 h 50 min, the return time of porpoises was 6 h, in comparison with 2.5 h after pingers had been silent. During the study period of approximately 50 days, habituation was detectable at two of nine PODs. The results indicate that pingers affect porpoises at greater distances than previously observed. This confirms that pingers are an effective bycatch mitigation measure, but alternative solutions should be applied in ecologically important habitats and migration routes. An example is given from the Baltic region.
A comparison of the heat shock response in juvenile and adult rainbow trout (Oncorhynchus mykiss) — implications for increased thermal sensitivity with age
Authors: Fowler Stephanie L. , Hamilton Diana , Currie Suzanne 
Published: January 2009

We conclude that the heat shock response is enhanced in juvenile compared with adult rainbow trout, Oncorhynchus mykiss . We have shown that the magnitude of the inducible heat shock response, as measured by increases in the heat shock protein (Hsp) Hsp70 is significantly greater in the hearts of fingerling than in adult trout following an acute (1 h) heat stress at 25 °C. Juvenile fish also express higher levels of constitutive Hsps (Hsc70, Hsp90) in their tissues, possibly reflecting higher rates of protein synthesis and increased chaperone function in this early life stage. This robust heat shock response in juvenile trout may contribute to a greater thermal resistance that is often observed in young salmonid fish.
Genetic isolation by distance and localized fjord population structure in Pacific cod (Gadus macrocephalus): limited effective dispersal in the northeastern Pacific Ocean
Authors: Cunningham Kathryn Maja , Canino Michael Francis , Spies Ingrid Brigette , Hauser Lorenz 
Published: January 2009

Genetic population structure of Pacific cod, Gadus macrocephalus , was examined across much of its northeastern Pacific range by screening variation at 11 microsatellite DNA loci. Estimates of FST(0.005 ± 0.002) and RST(0.010 ± 0.003) over all samples suggested that effective dispersal is limited among populations. Genetic divergence was highly correlated with geographic distance in an isolation-by-distance (IBD) pattern along the entire coastal continuum in the northeastern Pacific Ocean (~4000 km; r2= 0.83), extending from Washington State to the Aleutian Islands, and over smaller geographic distances for three locations in Alaska (~1700 km; r2= 0.56). Slopes of IBD regressions suggested average dispersal distance between birth and reproduction of less than 30 km. Exceptions to this pattern were found in samples taken from fjord environments in the Georgia Basin (the Strait of Georgia (Canada) and Puget Sound (USA)), where populations were differentiated from coastal cod. Our results showed population structure at spatial scales relevant to fisheries management, both caused by limited dispersal along the coast and by sharp barriers to migration isolating smaller stocks in coastal fjord environments.
A BARTH–LEFSCHETZ THEOREM FOR SUBMANIFOLDS OF A PRODUCT OF PROJECTIVE SPACES
Authors: BĂDESCU LUCIAN , REPETTO FLAVIA 
Published: January 2009

Let X be a complex submanifold of dimension d of ℙm × ℙn (m ≥ n ≥ 2) and denote by α: Pic(ℙm × ℙn) → Pic(X) the restriction map of Picard groups, by NX|ℙm × ℙn the normal bundle of X in ℙm × ℙn. Set t := max{dim π1(X), dim π2(X)}, where π1 and π2 are the two projections of ℙm × ℙn. We prove a Barth–Lefschetz type result as follows: Theorem. If [Formula: see text] then X is algebraically simply connected, the map α is injective and Coker(α) is torsion-free. Moreover α is an isomorphism if [Formula: see text], or if [Formula: see text] and NX|ℙm×ℙn is decomposable. These bounds are optimal. The main technical ingredients in the proof are: the Kodaira–Le Potier vanishing theorem in the generalized form of Sommese ([18, 19]), the join construction and an algebraization result of Faltings concerning small codimensional subvarieties in ℙN (see [9]).
ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells
Authors: Stankiewicz Monika J. , Crispino John D. 
Published: January 2009

Abstract
ETS2 and ERG are transcription factors, encoded on human chromosome 21 (Hsa21), that have been implicated in human cancer. People with Down syndrome (DS), who are trisomic for Hsa21, are predisposed to acute megakaryoblastic leukemia (AMKL). DS-AMKL blasts harbor a mutation in GATA1, which leads to loss of full-length protein but expression of the GATA-1s isoform. To assess the consequences of ETS protein misexpression on megakaryopoiesis, we expressed ETS2, ERG, and the related protein FLI-1 in wild-type and Gata1 mutant murine fetal liver progenitors. These studies revealed that ETS2, ERG, and FLI-1 facilitated the expansion of megakaryocytes from wild-type, Gata1-knockdown, and Gata1s knockin progenitors, but none of the genes could overcome the differentiation block characteristic of the Gata1-knockdown megakaryocytes. Although overexpression of ETS proteins increased the proportion of CD41+ cells generated from Gata1s-knockin progenitors, their expression led to a significant reduction in the more mature CD42 fraction. Serial replating assays revealed that overexpression of ERG or FLI-1 immortalized Gata1-knockdown and Gata1s knockin, but not wild-type, fetal liver progenitors. Immortalization was accompanied by activation of the JAK/STAT pathway, commonly seen in megakaryocytic malignancies. These findings provide evidence for synergy between alterations in GATA-1 and overexpression of ETS proteins in aberrant megakaryopoiesis.
Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma
Authors: Derom E. , Louis R. , Tiesler C. , Engelstätter R. , Kaufman J-M. , Joos G. F. 
Published: January 2009

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 µg·day−1and salmeterol 50 µg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design.All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC20) methacholine <8 mg·mL−1and a PC20adenosine <60 mg·mL−1. Primary outcome was 24-h serum cortisol suppression after 7 days. Secondary outcomes were changes in PC20methacholine and adenosine after 9 days.FP 500 µg·day−1and 1,000 µg·day−1significantly suppressed cortisol secretionversusplacebo by -46.2 (95% confidence interval (CI) -83.8– -8.5) nmol·L−1and by -76.1 (95% CI -112.9– -39.3) nmol·L−1, respectively. Neither dose of CIC (320 nor 640 µg·day−1) had a significant suppressive effect (-28.2 (95% CI -65.5–9.2) nmol·L−1and -37.3 (95% CI -74.7–0.0) nmol·L−1, respectively). Differences between FP 1,000 µg·day−1and both CIC treatments were statistically significant (CIC 320 µg·day−1: -48.0 (95% CI -84.8– -11.1) nmol·L−1; CIC 640 µg·day−1: -38.8 (95% CI -75.7– -1.9) nmol·L−1). Compared with placebo, the increase in PC20adenosine after the four treatments was small, but significant. Greater improvements in PC20adenosine were seen with FP 500 µg·day−1(1.8 (95% CI 1.0–2.6) doubling concentrations) compared with CIC 320 μg·day−1(0.9 (95% CI 0.1–1.7) doubling concentrations). No significant difference was seen between CIC 640 μg·day−1and FP 1,000 μg·day−1.For a similar decrease in hyperresponsiveness, cortisol secretion was suppressed significantly with moderate-to-high doses of fluticasone propionate, but not with ciclesonide.
Evaluation of allergic lung inflammation by computed tomography in a rat modelin vivo
Authors: Jobse B. N. , Johnson J. R. , Farncombe T. H. , Labiris R. , Walker T. D. , Goncharova S. , Jordana M. 
Published: January 2009

The ability of micro-computed tomography (CT) to noninvasively evaluate allergic pulmonary inflammation in an experimental model was investigated. In addition, two image segmentation methods and the value of respiratory gating were investigated in the context of this model.Brown Norway rats were exposed to one of four doses of house dust mite (HDM) extract (0, 0.15, 15 or 150 μg) delivered intratracheally every 24 h for 10 days. CT scanning was performed at baseline and after several longitudinal HDM exposures.Both thoracic- and lung-segmentation methods yielded similar results when standardisation practices were employed. While tissue histology correlated well with CT images, cell counts from bronchoalveolar lavage depicted greater inflammation than did density measures from CT images. Evidence from representative CT slices and transaxial density distribution indicated that inflammation was primarily associated with major airways and extended into the periphery from these focal points. Respiratory gating demonstrated that images of the inspiratory state provided greater contrast of inflammatory processes. Lastly, decreases in tidal volumes indicated significant mechanical respiratory changes in animals exposed to both 15 and 150 μg.In summary, CT image segmentation can extract pertinent data onin vivoallergic airway/lung inflammation. Furthermore, respiratory gating provides additional contrast and insight into these quantification practices.
Effect of heliox breathing on flow limitation in chronic heart failure patients
Authors: Pecchiari M. , Anagnostakos T. , D'Angelo E. , Roussos C. , Nanas S. , Koutsoukou A. 
Published: January 2009

Patients with chronic heart failure (CHF) exhibit orthopnoea and tidal expiratory flow limitation in the supine position. It is not known whether the flow-limiting segment occurs in the peripheral or central part of the tracheobronchial tree. The location of the flow-limiting segment can be inferred from the effects of heliox (80% helium/20% oxygen) administration. If maximal expiratory flow increases with this low-density mixture, the choke point should be located in the central airways, where the wave-speed mechanism dominates. If the choke point were located in the peripheral airways, where maximal flow is limited by a viscous mechanism, heliox should have no effect on flow limitation and dynamic hyperinflation.Tidal expiratory flow limitation, dynamic hyperinflation and breathing pattern were assessed in 14 stable CHF patients during air and heliox breathing at rest in the sitting and supine position.No patient was flow-limited in the sitting position. In the supine posture, eight patients exhibited tidal expiratory flow limitation on air. Heliox had no effect on flow limitation and dynamic hyperinflation and only minor effects on the breathing pattern.The lack of density dependence of maximal expiratory flow implies that, in CHF patients, the choke point is located in the peripheral airways.
FcϵRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells
Authors: Okayama Y. , Okumura S. , Sagara H. , Yuki K. , Sasaki T. , Watanabe N. , Fueki M. , Sugiyama K. , Takeda K. , Fukuda T. , Saito H. , Ra C. 
Published: January 2009

A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown.FcϵRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2±2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcϵRI-mediated TSLP mRNA expression (by 53.7±15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4±4.3 pg·mL−1to 121.5±3.7 pg·mL−1(p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001).Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcϵRI in the presence of IL-4.
Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD
Authors: Lomas D. A. , Silverman E. K. , Edwards L. D. , Locantore N. W. , Miller B. E. , Horstman D. H. , Tal-Singer R. 
Published: January 2009

Surfactant protein (SP)-D is a lung-derived protein that has been proposed as a biomarker for inflammatory lung disease.Serum SP-D was evaluated as a biomarker for components of chronic obstructive pulmonary disease (COPD) in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort and its response assessed to the administration of the anti-inflammatory agent prednisolone.The median level of serum SP-D was significantly elevated in 1,888 individuals with COPD compared to 296 current and former smokers without airflow obstruction (121.1 and 114.3 ng·mL−1, respectively; p = 0.021) and 201 nonsmokers (82.2 ng·ml−1; p<0.001). There was no correlation with the severity of COPD. Individuals with COPD who had a serum SP-D concentration that was greater than the 95th percentile of nonsmokers (175.4 ng·mL−1) showed an increased risk of exacerbations over the following 12 months (adjusted OR 1.30; 95% CI 1.03–1.63). Treatment with 20 mg·day−1prednisolone for 4 weeks resulted in a fall in serum SP-D levels (126.0 to 82.1 ng·mL−1; p<0.001) but no significant change in post-bronchodilator forced expiratory volume in 1 s.Serum SP-D concentration is raised in smokers and may be useful in identifying individuals who are at increased risk of exacerbations of COPD. It may represent an intermediate measure for the development of novel anti-inflammatory agents.