bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro
and
In Vivo
Antimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii
Authors: Antunes Luísa C. S. , Imperi Francesco , Minandri Fabrizia , Visca Paolo 
Published: September 2012

ABSTRACT

Multidrug-resistant
Acinetobacter baumannii
poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-
A. baumannii
chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO
3
)
3
, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58
A. baumannii
strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO
3
)
3
delayed the entry of
A. baumannii
into the exponential phase and drastically reduced bacterial growth rates. Ga(NO
3
)
3
activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO
3
)
3
also protected
Galleria mellonella
larvae from lethal
A. baumannii
infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO
3
)
3
inhibited the growth in human serum of 76% of the multidrug-resistant
A. baumannii
isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of
A. baumannii
bloodstream infections. Ga(NO
3
)
3
also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant
A. baumannii
.
Cysteine-Scanning Mutagenesis Supports the Importance of Clostridium perfringens Enterotoxin Amino Acids 80 to 106 for Membrane Insertion and Pore Formation
Authors: Chen Jianwu , Theoret James R. , Shrestha Archana , Smedley James G. , McClane Bruce A. 
Published: September 2012

ABSTRACT

Clostridium perfringens
enterotoxin (CPE) causes the gastrointestinal symptoms of the second most common bacterial food-borne illness. Previous studies suggested that a region named TM1, which has amphipathic characteristics and spans from amino acids 81 to 106 of the native CPE protein, forms a β-hairpin involved in β-barrel pore formation. To further explore the potential role of TM1 in pore formation, the single Cys naturally present in CPE at residue 186 was first altered to alanine by mutagenesis; the resultant rCPE variant, named C186A, was shown to retain cytotoxic properties. Cys-scanning mutagenesis was then performed in which individual Cys mutations were introduced into each TM1 residue of the C186A variant. When those Cys variants were characterized, three variants were identified that exhibit reduced cytotoxicity despite possessing binding and oligomerization abilities similar to those of the C186A variant from which they were derived. Pronase challenge experiments suggested that the reduced cytotoxicity of those two Cys variants, i.e., the F91C and F95C variants, which model to the tip of the β-hairpin, was attributable to a lessened ability of these variants to insert into membranes after oligomerization. In contrast, another Cys variant, i.e., the G103C variant, with impaired cytotoxicity apparently inserted into membranes after oligomerization but could not form a pore with a fully functional channel. Collectively, these results support the TM1 region forming a β-hairpin as an important step in CPE insertion and pore formation. Furthermore, this work identifies the first amino acid residues specifically involved in those two steps in CPE action.
Inflammatory Monocyte Recruitment Is Regulated by Interleukin-23 during Systemic Bacterial Infection
Authors: Indramohan Mohanalaxmi , Sieve Amy N. , Break Timothy J. , Berg Rance E. 
Published: September 2012

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that causes meningitis and septicemia in immunocompromised individuals and spontaneous abortion in pregnant women. The innate immune response againstL. monocytogenesis primarily mediated by neutrophils and monocytes. Interleukin-23 (IL-23) is an important proinflammatory cytokine well known for its role in neutrophil recruitment in various infectious and autoimmune diseases. We have previously shown that IL-23 is required for host resistance againstL. monocytogenesand for neutrophil recruitment to the liver, but not the spleen, during infection. Despite efficient neutrophil recruitment to the spleen, IL-23p19 knockout (KO) mice have an increased bacterial burden in this organ, suggesting that IL-23 may regulate the recruitment/function of another cell type to the spleen. In this study, we show that specific depletion of neutrophils abrogated the differences in bacterial burdens in the livers but not the spleens of C57BL/6 (B6) and IL-23p19 KO mice. Interestingly,L. monocytogenes-infected IL-23p19 KO mice had fewer monocytes in the spleen than B6 mice, as well as a reduction in the monocyte-recruiting chemokines CCL2 and CCL7. Additionally, the overall concentrations of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO•), as well as the percentages and total numbers of monocytes producing TNF-α and NO•, were reduced in IL-23p19 KO mice compared to levels in B6 mice, leading to increased bacterial burdens in the spleens ofL. monocytogenes-infected IL-23p19 KO mice. Collectively, our data establish that IL-23 is required for the optimal recruitment of TNF-α- and NO•-producing inflammatory monocytes, thus revealing a novel mechanism by which this proinflammatory cytokine provides protection against bacterial infection.
Kinetics of Innate Immune Response to Yersinia pestis after Intradermal Infection in a Mouse Model
Authors: Bosio Christopher F. , Jarrett Clayton O. , Gardner Donald , Hinnebusch B. Joseph 
Published: September 2012

ABSTRACTA hallmark ofYersinia pestisinfection is a delayed inflammatory response early in infection. In this study, we use an intradermal model of infection to study early innate immune cell recruitment. Mice were injected intradermally in the ear with wild-type (WT) or attenuatedY. pestislacking the pYV virulence plasmid (pYV−). The inflammatory responses in ear and draining lymph node samples were evaluated by flow cytometry and immunohistochemistry. As measured by flow cytometry, total neutrophil and macrophage recruitment to the ear in WT-infected mice did not differ from phosphate-buffered saline (PBS) controls or mice infected with pYV−, except for a transient increase in macrophages at 6 h compared to the PBS control. Limited inflammation was apparent even in animals with high bacterial loads (105to 106CFU). In addition, activation of inflammatory cells was significantly reduced in WT-infected mice as measured by CD11b and major histocompatibility complex class II (MHC-II) expression. When mice infected with WT were injected 12 h later at the same intradermal site with purified LPS,Y. pestisdid not prevent recruitment of neutrophils. However, significant reduction in neutrophil activation remained compared to that of PBS and pYV−controls. Immunohistochemistry revealed qualitative differences in neutrophil recruitment to the skin and draining lymph node, with WT-infected mice producing a diffuse inflammatory response. In contrast, focal sites of neutrophil recruitment were sustained through 48 h postinfection in pYV−-infected mice. Thus, an important feature ofY. pestisinfection is reduced activation and organization of inflammatory cells that is at least partially dependent on the pYV virulence plasmid.
Analysis of the Mechanisms That Underlie Absorption of Botulinum Toxin by the Inhalation Route
Authors: Al-Saleem Fetweh H. , Ancharski Denise M. , Joshi Suresh G. , Elias M. , Singh Ajay , Nasser Zidoon , Simpson Lance L. 
Published: September 2012

ABSTRACT
Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.
YbcL of Uropathogenic Escherichia coli Suppresses Transepithelial Neutrophil Migration
Authors: Lau Megan E. , Loughman Jennifer A. , Hunstad David A. 
Published: September 2012

ABSTRACT

Uropathogenic
Escherichia coli
(UPEC) strains suppress the acute inflammatory response in the urinary tract to ensure access to the intracellular uroepithelial niche that supports the propagation of infection. Our understanding of this initial cross talk between host and pathogen is incomplete. Here we report the identification of a previously uncharacterized periplasmic protein, YbcL, encoded by UPEC that contributes to immune modulation in the urinary tract by suppressing acute neutrophil migration. In contrast to wild-type UPEC, an isogenic strain lacking
ybcL
expression (UTI89 Δ
ybcL
) failed to suppress transepithelial polymorphonuclear leukocyte (PMN) migration
in vitro
, a defect complemented by expressing
ybcL
episomally. YbcL homologs are present in many
E. coli
genomes; expression of the YbcL variant encoded by nonpathogenic
E. coli
K-12 strain MG1655 (YbcL
MG
) failed to complement the UTI89 Δ
ybcL
defect, whereas expression of the UPEC YbcL variant (YbcL
UTI
) in MG1655 conferred the capacity for suppressing PMN migration. This phenotypic difference was due to a single amino acid difference (V78T) between the two YbcL homologs, and a majority of clinical UPEC strains examined were found to encode the suppressive YbcL variant. Purified YbcL
UTI
protein suppressed PMN migration in response to live or killed MG1655, and YbcL
UTI
was detected in the supernatant during UPEC infection of bladder epithelial cells or PMNs. Lastly, early PMN influx to murine bladder tissue was augmented upon
in vivo
infection with UTI89 Δ
ybcL
compared with wild-type UPEC. Our findings demonstrate a role for UPEC YbcL in suppression of the innate immune response during urinary tract infection.
The possible absence of a healthy-worker effect: a cross-sectional survey among educated Japanese women
Authors: Nishikitani Mariko , Nakao Mutsuhiro , Tsurugano Shinobu , Yano Eiji 
Published: September 2012

ObjectivesDespite being highly educated in comparison with women in other member countries of the Organisation for Economic Cooperation and Development, Japanese women are expected to assume traditional gender roles, and many dedicate themselves to full-time housewifery. Women working outside the home do so under poor conditions, and their health may not be better than that of housewives. This study compared the self-rated health status and health behaviours of housewives and working women in Japan.DesignCross-sectional survey.SettingA national university in Tokyo with 9864 alumnae.ParticipantsA total 1344 women who graduated since 1985 and completed questionnaires in an anonymous mail-based survey.Primary and secondary outcome measuresHealth anxiety and satisfaction, receipt of health check-ups, eating breakfast, smoking, and sleep problems according to job status and family demands: housewives (n=247) and working women with (n=624) and without (n=436) family demands. ORs were used for risk assessment, with housewives as a reference.ResultsAfter adjustment for satisfaction with present employment status and other confounding factors, working women were more likely than housewives to feel health anxiety (with family demands, OR: 1.68, 95% CI1.10 to 2.57; without family demands, OR: 3.57, 95% CI 2.19 to 4.50) and health dissatisfaction (without family demands, OR: 3.50, 95% CI 2.35 to 5.21); they were also more likely than housewives to eat an insufficient breakfast (with family demands, OR: 1.91, 95% CI 1.22 to 3.00; without family demands, OR: 4.02, 95% CI 2.47 to 6.57) and to have sleep problems (ORs: 2.08 to 4.03).ConclusionsNo healthy-worker effect was found among Japanese women. Housewives, at least those who are well educated, appear to have better health status and health-related behaviours than do working women with the same level of education.
Impact of a reduced red and processed meat dietary pattern on disease risks and greenhouse gas emissions in the UK: a modelling study
Authors: Aston Louise M , Smith James N , Powles John W 
Published: September 2012

ObjectivesConsumption of red and processed meat (RPM) is a leading contributor to greenhouse gas (GHG) emissions, and high intakes of these foods increase the risks of several leading chronic diseases. The aim of this study was to use newly derived estimates of habitual meat intakes in UK adults to assess potential co-benefits to health and the environment from reduced RPM consumption.DesignModelling study using dietary intake data from the National Diet and Nutrition Survey of British Adults.SettingBritish general population.MethodsRespondents were divided into fifths by energy-adjusted RPM intakes, with vegetarians constituting a sixth stratum. GHG emitted in supplying the diets of each stratum was estimated using data from life-cycle analyses. A feasible counterfactual UK population was specified, in which the proportion of vegetarians measured in the survey population doubled, and the remainder adopted the dietary pattern of the lowest fifth of RPM consumers.Outcome measuresReductions in risks of coronary heart disease, diabetes and colorectal cancer, and GHG emissions, under the counterfactual.ResultsHabitual RPM intakes were 2.5 times higher in the top compared with the bottom fifth of consumers. Under the counterfactual, statistically significant reductions in population aggregate risks ranged from 3.2% (95% CI 1.9 to 4.7) for diabetes in women to 12.2% (6.4 to 18.0) for colorectal cancer in men, with those moving from the highest to lowest consumption levels gaining about twice these averages. The expected reduction in GHG emissions was 0.45 tonnes CO2equivalent/person/year, about 3% of the current total, giving a reduction across the UK population of 27.8 million tonnes/year.ConclusionsReduced consumption of RPM would bring multiple benefits to health and environment.
Rates of obstetric intervention among low-risk women giving birth in private and public hospitals in NSW: a population-based descriptive study
Authors: Dahlen Hannah Grace , Tracy Sally , Tracy Mark , Bisits Andrew , Brown Chris , Thornton Charlene 
Published: September 2012

ObjectivesTo compare the risk profile of women giving birth in private and public hospitals and the rate of obstetric intervention during birth compared with previous published rates from a decade ago.DesignPopulation-based descriptive study.SettingNew South Wales, Australia.Participants691 738 women giving birth to a singleton baby during the period 2000 to 2008.Main outcome measuresRisk profile of women giving birth in public and private hospitals, intervention rates and changes in these rates over the past decade.ResultsAmong low-risk women rates of obstetric intervention were highest in private hospitals and lowest in public hospitals. Low-risk primiparous women giving birth in a private hospital compared to a public hospital had higher rates of induction (31% vs 23%); instrumental birth (29% vs 18%); caesarean section (27% vs 18%), epidural (53% vs 32%) and episiotomy (28% vs 12%) and lower normal vaginal birth rates (44% vs 64%). Low-risk multiparous women had higher rates of instrumental birth (7% vs 3%), caesarean section (27% vs 16%), epidural (35% vs 12%) and episiotomy (8% vs 2%) and lower normal vaginal birth rates (66% vs 81%). As interventions were introduced during labour, the rate of interventions in birth increased. Over the past decade these interventions have increased by 5% for women in public hospitals and by over 10% for women in private hospitals. Among low-risk primiparous women giving birth in private hospitals 15 per 100 women had a vaginal birth with no obstetric intervention compared to 35 per 100 women giving birth in a public hospital.ConclusionsLow-risk primiparous women giving birth in private hospitals have more chance of a surgical birth than a normal vaginal birth and this phenomenon has increased markedly in the past decade.
HIERARCHICAL-INTERPOLATIVE FUZZY SYSTEM CONSTRUCTION BY GENETIC AND BACTERIAL MEMETIC PROGRAMMING APPROACHES
Authors: BALÁZS KRISZTIÁN , KÓCZY LÁSZLÓ T. 
Published: September 2012

In this paper a family of new methods are proposed for constructing hierarchical-interpolative fuzzy rule bases in the frame of a fuzzy rule based supervised machine learning system modeling black box systems defined by input-output pairs. The resulting hierarchical rule base is constructed by using structure building pure evolutionary and memetic techniques, namely, Genetic and Bacterial Programming Algorithms and their memetic variants containing local search steps. Applying hierarchical-interpolative fuzzy rule bases is a rather efficient way of reducing the complexity of knowledge bases, whereas evolutionary methods (including memetic techniques) ensure a relatively fast convergence in the learning process. As it is presented in the paper, by applying a newly proposed representation schema these approaches can be combined to form hierarchical-interpolative machine learning systems.
CHECKING ORTHOGONAL TRANSFORMATIONS AND GENETIC ALGORITHMS FOR SELECTION OF FUZZY RULES BASED ON INTERPRETABILITY-ACCURACY CONCEPTS
Authors: REY M. ISABEL , GALENDE MARTA , FUENTE M. J. , SAINZ-PALMERO GREGORIO I. 
Published: September 2012

Fuzzy modeling is one of the most known and used techniques in different areas to model the behavior of systems and processes. In most cases, as in data-driven fuzzy modeling, these fuzzy models reach a high performance from the point of view of accuracy, but from other points of view, such as complexity or interpretability, they can present a poor performance. Several approaches are found in the bibliography to reduce the complexity and improve the interpretability of the fuzzy models. In this paper, a post-processing approach is carried out via rule selection, whose aim is to choose the most relevant rules for working together on the well-known accuracy-interpretability trade-off. The rule relevancy is based on Orthogonal Transformations, such as the SVD-QR rank revealing approach, the P-QR and OLS transformations. Rule selection is carried out using a genetic algorithm that takes into account the information obtained by the Orthogonal Transformations. The main objective is to check the true significance, drawbacks and advantages of the rule selection based on the orthogonal transformations via the rule firing strength matrix. In order to carry out this aim, a neuro-fuzzy system, FasArt (Fuzzy Adaptive System ART based), and several case studies, data sets from the KEEL Project Repository, are used to tune and check this selection of rules based on orthogonal transformations, genetic selection and accuracy-interpretability trade-off. This neuro-fuzzy system generates Mamdani fuzzy rule based systems (FRBSs), in an approximative way. NSGA-II is the MOEA tool used to tune the proposed rule selection.
Theory, analysis and applications of 2D global illumination
Authors: Jarosz Wojciech , Schönefeld Volker , Kobbelt Leif , Jensen Henrik Wann 
Published: September 2012

We investigate global illumination in 2D and show how this simplified problem domain leads to practical insights for 3D rendering.
We first derive a full theory of 2D light transport by introducing 2D analogs to radiometric quantities such as flux and radiance, and deriving a 2D rendering equation. We use our theory to show how to implement algorithms such as Monte Carlo raytracing, path tracing, irradiance caching, and photon mapping in 2D, and demonstrate that these algorithms can be analyzed more easily in this domain while still providing insights for 3D rendering.
We apply our theory to develop several practical improvements to the irradiance caching algorithm. We perform a full second-order analysis of diffuse indirect illumination, first in 2D, and then in 3D by deriving the irradiance Hessian, and show how this leads to increased accuracy and performance for irradiance caching. We propose second-order Taylor expansion from cache points, which results in more accurate irradiance reconstruction. We also introduce a novel error metric to guide cache point placement by analyzing the error produced by irradiance caching. Our error metric naturally supports anisotropic reconstruction and, in our preliminary study, resulted in an order of magnitude less error than the “split-sphere” heuristic when using the same number of cache points.