bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Mitochondrial Functions Associated with Azole Resistance in Candida glabrata Results in Enhanced Virulence in Mice
Authors: Ferrari Sélène , Sanguinetti Maurizio , De Bernardis Flavia , Torelli Riccardo , Posteraro Brunella , Vandeputte Patrick , Sanglard Dominique 
Published: February 2011

ABSTRACT

Mitochondrial dysfunction is one of the possible mechanisms by which azole resistance can occur in
Candida glabrata
. Cells with mitochondrial DNA deficiency (so-called “petite mutants”) upregulate ATP binding cassette (ABC) transporter genes and thus display increased resistance to azoles. Isolation of such
C. glabrata
mutants from patients receiving antifungal therapy or prophylaxis has been rarely reported. In this study, we characterized two sequential and related
C. glabrata
isolates recovered from the same patient undergoing azole therapy. The first isolate (BPY40) was azole susceptible (fluconazole MIC, 4 μg/ml), and the second (BPY41) was azole resistant (fluconazole MIC, >256 μg/ml). BPY41 exhibited mitochondrial dysfunction and upregulation of the ABC transporter genes
C. glabrata CDR1
(
CgCDR1
),
CgCDR2
, and
CgSNQ2
. We next assessed whether mitochondrial dysfunction conferred a selective advantage during host infection by testing the virulence of BPY40 and BPY41 in mice. Surprisingly, even with
in vitro
growth deficiency compared to BPY40, BPY41 was more virulent (as judged by mortality and fungal tissue burden) than BPY40 in both systemic and vaginal murine infection models. The increased virulence of the petite mutant correlated with a drastic gain of fitness in mice compared to that of its parental isolate. To understand this unexpected feature, genome-wide changes in gene expression driven by the petite mutation were analyzed by use of microarrays during
in vitro
growth. Enrichment of specific biological processes (oxido-reductive metabolism and the stress response) was observed in BPY41, all of which was consistent with mitochondrial dysfunction. Finally, some genes involved in cell wall remodelling were upregulated in BPY41 compared to BPY40, which may partially explain the enhanced virulence of BPY41. In conclusion, this study shows for the first time that mitochondrial dysfunction selected
in vivo
under azole therapy, even if strongly affecting
in vitro
growth characteristics, can confer a selective advantage under host conditions, allowing the
C. glabrata
mutant to be more virulent than wild-type isolates.
Synergism between Outer Membrane Proteins and Antimicrobials
Authors: Veiga-Crespo P. , Fusté E. , Vinuesa T. , Viñas M. , Villa T. G. 
Published: February 2011

ABSTRACT

Antibiotic-resistant bacteria are becoming one of the most important problems in health care because of the number of resistant strains and the paucity of new effective antimicrobials. Since antibiotic-resistant bacteria will continue to increase, it is necessary to look for new alternative strategies to fight against them. It is generally accepted that Gram-negative bacteria are intrinsically less susceptible than Gram-positive bacteria to antimicrobials. The main reason is that Gram-negative bacteria are surrounded by a permeability barrier known as the outer membrane (OM). Hydrophilic solutes most often cross the OM through water-filled channels formed by a particular family of proteins known as porins. This work explores the possibility of using exogenous porins to lower the required amounts of antibiotics (ampicillin, ciprofloxacin, cefotaxime, clindamycin, erythromycin, and tetracycline). Porins had a bactericidal effect on
Escherichia coli
cultures, mainly in the logarithmic phase of growth, when combined with low antibiotic concentrations. The use of different antibiotic-porin mixtures showed a bactericidal effect greater than those of antibiotics and porins when used separately. It was possible to observe different behaviors according to the antibiotic type used.
Immunoregulatory Cytokines Are Associated with Protection from Immunopathology following Mycobacterium avium Subspecies paratuberculosis Infection in Red Deer
Authors: Robinson M. W. , O'Brien R. , Mackintosh C. G. , Clark R. G. , Griffin J. F. T. 
Published: February 2011

ABSTRACTAlthough the causative agent of Johne's disease,Mycobacterium aviumsubsp.paratuberculosis, is well known, the etiology of disease and the immune responses generated in response to infection are still poorly understood. Knowledge of definitive markers of protective immunity, infection, and the establishment of chronic granulomatous Johne's disease is necessary to advance vaccine and diagnostic development. We sought to profile the immune responses occurring within jejunal lymph nodes of experimentally challenged red deer (Cervus elaphus). Quantitative PCR was utilized to measure a range of cytokines, signaling molecules, and transcription factors involved in Th1, Th2, Treg, and Th17 immune responses. Significant differences in gene expression were observed between control, minimally diseased, and severely diseased animals, with severely diseased animals showing elevated proinflammatory transcripts and reduced anti-inflammatory transcripts. We identified a proinflammatory cytokine milieu of gamma interferon, interleukin-1α (IL-1α), and IL-17, which may contribute to the immunopathology observed during clinical Johne's disease and suggest that Th2 and Treg immune responses may play an important role in controlling the development of immunopathology in infected animals.
Protein Kinase LegK2 Is a Type IV Secretion System Effector Involved in Endoplasmic Reticulum Recruitment and Intracellular Replication of Legionella pneumophila
Authors: Hervet Eva , Charpentier Xavier , Vianney Anne , Lazzaroni Jean-Claude , Gilbert Christophe , Atlan Danièle , Doublet Patricia 
Published: February 2011

ABSTRACT

Legionella pneumophila
is the etiological agent of Legionnaires' disease. Crucial to the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuoles within host cells. The Dot/Icm type IV secretion system (T4SS), which translocates a large number of bacterial effectors into host cell, is absolutely required for rerouting the
Legionella
phagosome. Many
Legionella
effectors display distinctive eukaryotic domains, among which are protein kinase domains.
In silico
analysis and
in vitro
phosphorylation assays identified five functional protein kinases, LegK1 to LegK5, encoded by the epidemic
L. pneumophila
Lens strain. Except for LegK5, the
Legionella
protein kinases are all T4SS effectors. LegK2 plays a key role in bacterial virulence, as demonstrated by gene inactivation. The
legK2
mutant containing vacuoles displays less-efficient recruitment of endoplasmic reticulum markers, which results in delayed intracellular replication. Considering that a kinase-dead substitution mutant of
legK2
exhibits the same virulence defects, we highlight here a new molecular mechanism, namely, protein phosphorylation, developed by
L. pneumophila
to establish a replicative niche and evade host cell defenses.
A high-density genetic linkage map of a black spruce (Picea mariana) × red spruce (Picea rubens) interspecific hybrid
Authors: Kang Bum-Yong , Major John E. , Rajora Om P. 
Published: February 2011

Genetic maps provide an important genomic resource of basic and applied significance. Spruce ( Picea ) has a very large genome size (between 0.85 × 1010and 2.4 × 1010bp; 8.5–24.0 pg/1C, a mean of 17.7 pg/1C ). We have constructed a near-saturated genetic linkage map for an interspecific backcross (BC1) hybrid of black spruce (BS; Picea mariana (Mill.) B.S.P.) and red spruce (RS; Picea rubens Sarg.), using selectively amplified microsatellite polymorphic loci (SAMPL) markers. A total of 2284 SAMPL markers were resolved using 31 SAMPL–MseI selective nucleotide primer combinations. Of these, 1216 SAMPL markers showing Mendelian segregation were mapped, whereas 1068 (46.8%) SAMPL fragments showed segregation distortion at α = 0.05. Maternal, paternal, and consensus maps consistently coalesced into 12 linkage groups, corresponding to the haploid chromosome number (1n = 1x = 12) of 12 in the genus Picea. The maternal BS map consisted of 814 markers distributed over 12 linkage groups, covering 1670 cM, with a mean map distance of 2.1 cM between adjacent markers. The paternal BS × RS map consisted of 773 markers distributed over 12 linkage groups, covering 1563 cM, with a mean map distance of 2.0 cM between adjacent markers. The consensus interspecific hybrid BC1map consisted of 1216 markers distributed over 12 linkage groups, covering 1865 cM (98% genome coverage), with a mean map distance of 1.5 cM between adjacent markers. The genetic map reported here provides an important genomic resource in Picea, Pinaceae, and conifers.
Analysis of allelic differential expression in the human genome using allele-specific serial analysis of gene expression tags
Authors: Vidal Daniel Onofre , de Souza Jorge Estefano S. , Pires Lilian Campos , Masotti Cibele , Salim Anna Christina Matos , Costa Maria Cristina Ferreira , Galante Pedro Alexandre Favoretto , de Souza Sandro José , Camargo Anamaria Aranha 
Published: February 2011

Recent reports have demonstrated that a significant proportion of human genes display allelic differential expression (ADE). ADE is associated with phenotypic variability and may contribute to complex genetic diseases. Here, we present a computational analysis of ADE using allele-specific serial analysis of gene expression (SAGE) tags representing 1295 human genes. We identified 472 genes for which unequal representation (>3-fold) of allele-specific SAGE tags was observed in at least one SAGE library, suggesting the occurrence of ADE. For 235 out of these 472 genes, the difference in the expression level between both allele-specific SAGE tags was statistically significant (p < 0.05). Eleven candidate genes were then subjected to experimental validation and ADE was confirmed for 8 out of these 11 genes. Our results suggest that at least 25% of the human genes display ADE and that allele-specific SAGE tags can be efficiently used for the identification of such genes.
Exercise-induced protection of bone marrow cells following exposure to radiation
Authors: De Lisio Michael , Phan Nghi , Boreham Douglas R. , Parise Gianni 
Published: February 2011

The hormetic effects of exercise training have previously been shown to enhance cellular protection against oxidative stress. Therefore, adaptations to exercise training may attenuate the harmful effects of radiation induced by oxidative stress. Flow cytometric analysis of genotoxicity (γH2AX foci and micronucleated reticulocytes (MN-RET)) and cytotoxicity (apoptosis and percentage of reticulocytes) were conducted on bone marrow cells isolated from acutely exercised (Acute EX), exercise-trained (EX), and sedentary (SED) mice following 1 and 2 Gy radiation challenges in vitro. Acute EX increased the percentage of cells with activated caspase-3 and -7 (32%, p < 0.001) and γH2AX foci formation in response to 2 Gy radiation challenge (10%, p < 0.05). Exercise training significantly attenuated γH2AX foci formation and MN-RET production in response to 1 Gy radiation challenge (18%, p < 0.05 and 22%, p < 0.05, respectively). Exercise training also significantly reduced basal percentages of cells with activated caspase-3 and -7 and in response to radiation in bone marrow cells (11%, p < 0.05). These results suggest that oxidative stress caused by acute exercise induces an adaptive response responsible for the radioprotective effects of exercise training.
Changes in calcium status in aged rats fed Lactobacillus GG and Bifidobacterium lactis and oligofructose-enriched inulin
Authors: Naughton Violetta , McSorley Emeir , Naughton Patrick J. 
Published: February 2011

In this study we hypothesized that an increase in numbers of beneficial bacteria in the large intestine can affect calcium (Ca) status in the elderly. Adult and aged rats were fed a diet with or without synbiotics for 21 days. Synbiotics increased the numbers of lactobacilli and bifidobacteria in large intestine in both adult and aged rats. The plasma Ca concentration was significantly increased while osteocalcin concentration was significantly decreased only in aged rats fed synbiotics.
NF-κB activation in organs from STZ-treated rats
Authors: Locke Marius , Anderson Jocelyn 
Published: February 2011

Nuclear factor kappa B (NF-κB) is a ubiquitously expressed transcription factor comprised of various subunits (p50 (NF-κB1), p52 (NF-κB2), p65 (RelA), RelB, and c-Rel). Activation of certain NF-κB subunits appears to foster an inflammatory state that may promote the development of disease. Thus characterizing the specific NF-κB subunits may provide insight into the pathogenesis of certain diseases. The purpose of this study was to determine if 1 month of a diabetic state, induced by streptozotocin (STZ) treatment, alters the constitutive level of NF-κB activation, its subunit composition, or the content of NF-κB-related proteins in rodent liver, kidney, spleen, and heart. Diabetes was induced in male Sprague–Dawley rats by a single tail vein injection of STZ (55 mg·kg–1body weight). After 30 days, the heart, liver, spleen, and kidney were assessed for NF-κB activation and subunit composition with electrophoretic mobility shift assay (EMSA), and p50 and p65 subunit content was assessed with Western blotting. In diabetic animals, the constitutive level of NF-κB activation was reduced in liver, but was unchanged in kidney, spleen, and heart. EMSA supershifts showed the predominant subunit in the activated NF-κB complexes from both diabetic and control animals to be p50, although the p65 subunit was detected in NF-κB complexes from diabetic hearts. The content of p50 was unaltered in all diabetic tissues examined, whereas the content of p65 was increased only in hearts from diabetic animals. These findings support the idea that a diabetic state may induce specific changes in NF-κB subunit composition in certain tissues.
Association between exercise hemodynamics and changes in local vascular function following acute exercise
Authors: Gonzales Joaquin U. , Thompson Benjamin C. , Thistlethwaite John R. , Scheuermann Barry W. 
Published: February 2011

Skeletal muscle contractions are associated with physical stimuli that act upon muscle vasculature, including increased shear stress and blood pressure. It is unclear if acute dynamic exercise alters local vascular function. The purpose of this study was to examine the role of exercise hemodynamics on the effects of acute exercise on vascular function, as evaluated by brachial artery flow-mediated dilation (FMD). Healthy individuals (n = 14; age, 18–34 years) performed 30 min of handgrip exercise at fast and slow contractions. Blood pressure during exercise was measured using a Vasotrac system (Medwave Inc.), while shear rate during exercise and FMD at rest and after 30 min of recovery from exercise were measured in the brachial artery of the active arm using Doppler ultrasound. Estimated contractile work was correlated with blood pressure (r = 0.61, p < 0.01) and retrograde shear rate (r = –0.78, p < 0.01). As a result, blood pressure was higher (p < 0.05) and oscillatory shear index was lower (p < 0.05) during slow as compared with fast contractions. On average, FMD was unchanged following fast contractions (5.4 ± 3.4%dilation to 6.1 ± 3.8%dilation; p = 0.19), but significantly reduced following slow contractions (6.9 ± 4.2%dilation to 3.6 ± 2.5%dilation; p = 0.01). Within slow contractions, subgroup analysis revealed blood pressure to associate with the change in FMD; such that individuals with mean blood pressure >100 mm Hg (range, 102–139 mm Hg) during exercise had larger decreases in FMD than individuals with lower exercise blood pressure. These results indicate that impaired local vascular function following acute exercise with high contractile activity is associated with blood pressure stimuli in healthy individuals
Prevalence of putative virulence markers inCampylobacter jejuniandCampylobacter coliisolated from hospitalized children, raw chicken, and raw beef in Tehran, Iran
Authors: Hamidian Mohammad , Sanaei Maryam , Bolfion Mehdi , Dabiri Hossein , Zali Mohammad-Reza , Walther-Rasmussen Jan 
Published: February 2011

The incidence of the virulence-associated genes cdtA, cdtB, cdtC, cadF, dnaJ, racR, and pldA has been investigated in Campylobacter jejuni and Campylobacter coli collected from raw chicken and beef from retailers in Tehran, Iran, and from hospitalized children (age, ≤14 years) suffering from diarrhea. Campylobacter spp. were collectively identified by morphological and biochemical methods. Campylobacter jejuni and C. coli were discriminated from other Campylobacter spp. by amplification of a specific conserved fragment of the 16S rRNA gene. The distinction between C. jejuni and C. coli was subsequently made by molecular determination of the presence of the hipO gene in C. jejuni or the ask gene in C. coli. Fragments of the studied virulence-associated genes, cdtA, cdtB, cdtC, cadF, racR, dnaJ, and pldA, were amplified by PCR and subjected to horizontal gel electrophoresis. A total of 71 isolates of C. jejuni and 24 isolates of C. coli from meat were analyzed, while the numbers of isolates from the hospitalized children were 28 and 9, respectively. The unequal distribution of C. jejuni and C. coli in the samples has also been reported in other studies. Statistical analyses by the use of the two-tailed Fisher’s exact test of the occurrence of the virulence genes in the isolates of different origins showed that the occurrence of the dnaJ gene was consistently significantly higher in all C. jejuni isolates than in C. coli. The occurrence of the other virulence markers did not differ significantly between species in the majority of the isolates. The PCR results also showed that the occurrence of the virulence markers in the analyzed isolates was much lower than in other studies, which may be caused by a divergent genomic pool of our isolates in comparison with others.
Intraspecific comparison of diet of California sea lions (Zalophus californianus) assessed using fecal and stable isotope analyses
Authors: Orr A. J. , VanBlaricom G. R. , DeLong R. L. , Cruz-Escalona V. H. , Newsome S. D. 
Published: February 2011

The diet of juvenile and adult female California sea lions ( Zalophus californianus (Lesson, 1828)) at San Miguel Island, California, was estimated and compared using fecal and stable isotope analyses to determine dietary differences by age. Fecal samples were collected during 2002–2006 and prey remains were identified. Stable carbon (δ13C) and stable nitrogen (δ15N) isotope values were determined from plasma and fur obtained from yearlings, 2- to 3-year-old juveniles, and adult females during 2005 and 2006. Juveniles ate more than 15 prey taxa, whereas adult females consumed more than 33 taxa. Relative importance of prey was determined using percent frequency of occurrence (%FO). Engraulis mordax Girard, 1854, Sardinops sagax (Jenyns, 1842), Merluccius productus (Ayres, 1855), genus Sebastes Cuvier, 1829, and Loligo opalescens Berry, 1911 were the most frequently occurring (%FO > 10%) prey in the feces of both juvenile and adult female sea lions, although their importance varied between age groups. Only yearlings had significantly different isotopic values than older conspecifics, indicating that older juveniles were feeding at a similar trophic level and in similar habitats as adult females. Whereas each method had biases, combining the two provided a better understanding of the diet of California sea lions and intraspecific differences.
Quality of mature aspen and maple forests for breeding Yellow-bellied Sapsuckers (Sphyrapicus varius)
Authors: Tozer Douglas C. , Nol Erica , Burke Dawn M. 
Published: February 2011

Mature aspen (genus Populus L..) and maple (genus Acer L.) forests appear to be high-quality breeding habitat for Yellow-bellied Sapsuckers ( Sphyrapicus varius (L., 1766)). To explore some of the mechanisms that influence quality of the breeding habitat, we measured demographic and breeding resources in four forest stands each of 95-year-old quaking aspen ( Populus tremuloides Michx.) and 182-year-old sugar maple ( Acer saccharum Marsh.) in Algonquin Provincial Park, Ontario, from 2007 to 2009. Population density was higher, egg laying earlier, clutches larger, hatching success greater, and per capita and population fledgling production higher in maple stands compared with aspen stands. Longer nest-building and prelaying stages in aspen stands delayed egg laying by 5 days relative to maple stands. The delay in egg laying in aspen stands may have been caused by lower quality sap resources, which then resulted in lower productivity. Adults delivered smaller food loads to nests in aspen stands than in maple stands, which may have increased nestling mortality in aspen stands. Although per capita fledgling production was lower in aspen stands than in maple stands, Yellow-bellied Sapsuckers in both forests were able to replace themselves, suggesting that mature deciduous and mixed-deciduous forests, in general, are high-quality breeding habitat for this sapsucker.
PRODUCTION AND SEARCHES FOR CASCADE BARYONS WITH CLAS
Authors:   For the CLAS Collaboration, Smith Elton S. 
Published: February 2011

We present the results of photoproduction cross sections of the ground state cascade Ξ- and the first excited state Ξ*-(1530) measured with the CLAS detector. The photoproduction of the cascade resonances has been investigated in the reactions γp → K+K+(X) and γp → K+K+π-(X). The differential and total cross sections of the Ξ- were determined for photon beam energies from 2.75 to 4.75 GeV and are consistent with a production mechanism of Y* → K+Ξ- through a t-channel process. The cross-section of the Ξ*-(1530) has been determined for photon beam energies from 3.35 to 4.75 GeV. The reaction γp → K+K+π-(Ξ0) has also been investigated in the search for excited cascade resonances decaying to π-Ξ0. No significant signal of excited cascade states other than the well-known Ξ*-(1530) is observed. We also present the latest results of a search for the Φ--(1862) exotic pentaquark state in a photoproduction experiment on a deuterium target. A high-statistics sample of π-Ξ- events have been collected and analyzed. A preliminary invariant mass spectrum of the π-Ξ- system is presented, which is used to set upper limits on the photoproduction of the Φ-- pentaquark state.
Abstract delta modeling
Authors: Clarke Dave , Helvensteijn Michiel , Schaefer Ina 
Published: February 2011

Delta modeling is an approach to facilitate automated product derivation for software product lines. It is based on a set of deltas specifying modifications that are incrementally applied to a core product. The applicability of deltas depends on feature-dependent conditions. This paper presents abstract delta modeling, which explores delta modeling from an abstract, algebraic perspective.
Compared to previous work, we take a more flexible approach with respect to conflicts between modifications and introduce the notion of conflict-resolving deltas. We present conditions on the structure of deltas to ensure unambiguous product generation.