bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activities of Dalbavancin against a Worldwide Collection of 81,673 Gram-Positive Bacterial Isolates
Authors: Biedenbach Douglas J. , Bell Jan M. , Sader Helio S. , Turnidge John D. , Jones Ronald N. 
Published: January 2009

ABSTRACTDalbavancin, a long-acting lipoglycopeptide, was evaluated against 81,673 isolates of staphylococci, enterococci, and streptococci collected from 33 countries during worldwide resistance surveillance (2002 to 2007). Regardless of susceptibility to oxacillin, comparable potencies for dalbavancin againstStaphylococcus aureusand coagulase-negative staphylococci from all countries were noted (MIC90, 0.06 to 0.12 μg/ml). Vancomycin-susceptibleEnterococcusspp. had dalbavancin MIC90s comparable to those for staphylococci, whereas vancomycin-resistant strains were more resistant (MIC50, >4 μg/ml). β-Hemolytic and viridians group streptococci were very susceptible to dalbavancin (MIC90, ≤0.03 μg/ml). Overall, dalbavancin was ≥16-fold more active than vancomycin against the monitored gram-positive species.
A Pseudouridine Synthase Homologue Is Critical to Cellular Differentiation inToxoplasma gondii
Authors: Anderson Matthew Z. , Brewer Jeremy , Singh Upinder , Boothroyd John C. 
Published: January 2009

ABSTRACTToxoplasma gondiiis a haploid protozoan parasite infecting about one in seven people in the United States. Key to the worldwide prevalence ofT. gondiiis its ability to establish a lifelong, chronic infection by evading the immune system, and central to this is the developmental switch between the two asexual forms, tachyzoites and bradyzoites. A library of mutants defective in tachyzoite-to-bradyzoite differentiation (Tbd−) was created through insertional mutagenesis. This library contains mutants that, compared to the wild type, are between 20% and 74% as efficient at stage conversion. Two mutants, TBD5 and TBD8, with disruptions in a gene encoding a putative pseudouridine synthase, PUS1, were identified. The disruption in TBD8 is in the 5′ end of thePUS1gene and appears to produce a null allele with a 50% defect in differentiation. This is about the same switch efficiency as obtained with an engineeredpus1deletion mutant (Δpus1). The insertion in TBD5 is within thePUS1coding region, and this appears to result in a more extreme phenotype of only ∼10% switch efficiency. Complementation of TBD8 with the genomicPUS1allele restored wild-type differentiation efficiency. Infection of mice withpus1mutant strains results in increased mortality during the acute phase and higher cyst burdens during the chronic infection, demonstrating an aberrant differentiation phenotype in vivo due toPUS1disruption. Our results suggest a surprising and important role for RNA modification in this biological process.
The
Schistosoma mansoni
Protein Sm16/SmSLP/SmSPO-1 Assembles into a Nine-Subunit Oligomer with Potential To Inhibit Toll-Like Receptor Signaling
Authors: Brännström Kristoffer , Sellin Mikael E. , Holmfeldt Per , Brattsand Maria , Gullberg Martin 
Published: January 2009

ABSTRACT

The Sm16/SmSLP/SmSPO-1 (Sm16) protein is secreted by the parasite
Schistosoma mansoni
during skin penetration and has been ascribed immunosuppressive activities. Here we describe the strategy behind the design of a modified Sm16 protein with a decreased aggregation propensity, thus facilitating the expression and purification of an Sm16 protein that is soluble in physiological buffers. The Stokes radii and sedimentation coefficients of recombinant and native proteins indicate that Sm16 is an approximately nine-subunit oligomer. Analysis of truncated Sm16 derivatives showed that both oligomerization and binding to the plasma membrane of human cells depend on multiple C-terminal regions. For analysis of immunomodulatory activities, Sm16 was expressed in
Pichia pastoris
to facilitate the preparation of a pyrogen/endotoxin-free purified protein. Recombinant Sm16 was found to have no effect on T-lymphocyte activation, cell proliferation, or the basal level of cytokine production by whole human blood or monocytic cells. However, Sm16 exerts potent inhibition of the cytokine response to the Toll-like receptor (TLR) ligands lipopolysaccharide (LPS) and poly(I:C) while being less efficient at inhibiting the response to the TLR ligand peptidoglycan or a synthetic lipopeptide. Since Sm16 specifically inhibits the degradation of the IRAK1 signaling protein in LPS-stimulated monocytes, our findings indicate that inhibition is exerted proximal to the TLR complex.
Contact-Dependent Growth Inhibition Causes Reversible Metabolic Downregulation in
Escherichia coli
Authors: Aoki S. K. , Webb J. S. , Braaten B. A. , Low D. A. 
Published: January 2009

ABSTRACT

Contact-dependent growth inhibition (CDI) is a mechanism identified in
Escherichia coli
by which bacteria expressing two-partner secretion proteins encoded by
cdiA
and
cdiB
bind to BamA in the outer membranes of target cells and inhibit their growth. A third gene in the cluster,
cdiI
, encodes a small protein that is necessary and sufficient to confer immunity to CDI, thereby preventing cells expressing the
cdiBA
genes from inhibiting their own growth. In this study, the
cdiI
gene was placed under
araBAD
promoter control to modulate levels of the immunity protein and thereby induce CDI by removal of arabinose. This CDI autoinhibition system was used for metabolic analyses of a single population of
E. coli
cells undergoing CDI. Contact-inhibited cells showed altered cell morphology, including the presence of filaments. Notably, CDI was reversible, as evidenced by resumption of cell growth and normal cellular morphology following induction of the CdiI immunity protein. Recovery of cells from CDI also required an energy source. Cells undergoing CDI showed a significant, reversible downregulation of metabolic parameters, including aerobic respiration, proton motive force (Δp), and steady-state ATP levels. It is unclear whether the decrease in respiration and/or Δp is directly involved in growth inhibition, but a role for ATP in the CDI mechanism was ruled out using an
atp
mutant. Consistent with the observed decrease in Δp, the phage shock response was induced in cells undergoing CDI but not in recovering cells, based on analysis of levels of
pspA
mRNA.
The Salmonella Pathogenicity Island (SPI) 1 contributes more than SPI2 to the colonization of the chicken by Salmonella enterica serovar Typhimurium
Authors: Dieye Yakhya , Ameiss Keith , Mellata Melha , Curtiss Roy 
Published: January 2009

Abstract

Background

Salmonella enterica serovar Typhimurium (Typhimurium) is an important pathogen that infects a broad range of hosts. In humans, Typhimurium causes a gastroenteritis characterized by vomiting, diarrhea, and abdominal pains. Typhimurium infection occurs mainly through the ingestion of contaminated food including poultry, pork, eggs, and milk. Chickens that are asymptomatic carriers of Typhimurium constitute a potential reservoir for infection. The type three secretion systems encoded by Salmonella pathogenicity islands (SPI) 1 and 2 are major virulence factors of Salmonella. However, only a few studies have investigated their role during the infection of chickens.

Results
We have taken a mixed infection approach to study the contribution of SPI1 and SPI2 to the colonization of the chicken by Typhimurium. We found that SPI1 contributes to colonization of both the cecum and spleen in the chicken. In contrast, SPI2 contributes to colonization of the spleen but not the cecum and, in the absence of SPI1, inhibits cecal colonization. Additionally, we show that the contribution of SPI1 in the spleen is greater than that of SPI2. These results are different from those observed during the infection of the mouse by Typhimurium where SPI2 is the major player during systemic colonization.

Conclusion
The co-infection model we used provides a sensitive assay that confirms the role of SPI1 and clarifies the role of SPI2 in the colonization of the chicken by Typhimurium.
Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells
Authors: Scharer Christopher D , Laycock Noelani , Osunkoya Adeboye O , Logani Sanjay , McDonald John F , Benigno Benedict B , Moreno Carlos S 
Published: January 2009

AbstractBackgroundA large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer. Recent data has shown that overexpression of Aurora-A can confer resistance to the taxane paclitaxel.MethodsWe used expression profiling of ovarian tumor samples to determine the most significantly overexpressed genes. In this study we sought to determine if chemical inhibition of the Aurora kinase family using VE-465 could synergize with paclitaxel to induce apoptosis in paclitaxel-resistant and sensitive ovarian cancer cells.ResultsAurora-A kinase and TPX2, an activator of Aurora-A, are two of the most significantly overexpressed genes in ovarian carcinomas. We show that inhibition of the Aurora kinases prevents phosphorylation of a mitotic marker and demonstrate a dose-dependent increase of apoptosis in treated ovarian cancer cells. We demonstrate at low doses that are specific to Aurora-A, VE-465 synergizes with paclitaxel to induce 4.5-fold greater apoptosis than paclitaxel alone in 1A9 cells. Higher doses are needed to induce apoptosis in paclitaxel-resistant PTX10 cells.ConclusionOur results show that VE-465 is a potent killer of taxane resistant ovarian cancer cells and can synergize with paclitaxel at low doses. These data suggest patients whose tumors exhibit high Aurora-A expression may benefit from a combination therapy of taxanes and Aurora-A inhibition.
Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia
Authors: Sondag Cindy M , Dhawan Gunjan , Combs Colin K 
Published: January 2009

Abstract

Background
Beta amyloid (Aβ) peptides are the major constituents of the senile plaques present in Alzheimer's diseased brain. Pathogenesis has been associated with the aggregated form of the peptide as these fibrils are the conformation readily found in the plaques. However, recent studies have shown that the nonaggregated, soluble assemblies of Aβ have the potential to stimulate neuronal dysfunction and may play a prominent role in the pathogenesis of Alzheimer's disease.

Methods
Soluble, synthetic Aβ1–42 oligomers were prepared producing mainly dimer-trimer conformations as assessed by SDS-PAGE. Similar analysis demonstrated fibril preparations to produce large insoluble aggregates unable to migrate out of the stacking portion of the gels. These peptide preparations were used to stimulate primary murine microglia and cortical neuron cultures. Microglia were analyzed for changes in signaling response and secretory phenotype via Western analysis and ELISA. Viability was examined by quantifying lactate dehydrogenase release from the cultures.

Results
Aβ oligomers and fibrils were used to stimulate microglia for comparison. Both the oligomers and fibrils stimulated proinflammatory activation of primary microglia but the specific conformation of the peptide determined the activation profile. Oligomers stimulated increased levels of active, phosphorylated Lyn and Syk kinase as well as p38 MAP kinase compared to fibrils. Moreover, oligomers stimulated a differential secretory profile for interleukin 6, monocyte chemoattractant protein-1 and keratinocyte chemoattractant when compared to fibrils. Finally, soluble oligomers stimulated death of cultured cortical neurons that was exacerbated by the presence of microglia.

Conclusion
These data suggest that fibrils and oligomers stimulate unique signaling responses in microglia leading to discrete secretory changes and effects on neuron survival. This suggests that inflammation changes during disease may be the consequence of unique peptide-stimulated events and each conformation may represent an individual anti-inflammatory therapeutic target.
Nonconstrictive epicarditis mimicking a cardiac mass in a 71-year-old Caucasian man: a case report and review of the literature
Authors: Margolis Asa M , Emmerman Andrew B , Rascon Mario , Chaudhry Saima I 
Published: January 2009

Abstract

Introduction
Isolated cases of epicarditis are rare. Thus far, all have occurred with constrictive physiology as most cases involve both parietal and visceral pericardium. We report the first case of asymptomatic epicarditis that involved only the visceral pericardium presenting without constrictive physiology.

Case presentation
A 71-year-old male with a history of atrial fibrillation, coronary artery disease, pericardial effusion, type-2 diabetes and hypothyroidism presented with 5 weeks of fatigue and 1 day of dizziness. Physical examination was significant for pallor and tachycardia. Laboratory analysis revealed a hemoglobin count of 7.2 g/dl and iron deficiency anemia. The patient was transfused and evaluated by endoscopic ultrasound. A polypoid mass in the gastric cardia was found and later diagnosed as gastric adenocarcinoma (staged as T1N0M0). The pericardial effusion was evaluated with transthoracic echocardiography which showed a 2.0 × 2.7 cm mass associated with the right atrium. Transesophageal echocardiography confirmed the mass but did not reveal constrictive physiology. Whole-body contrast computed tomography failed to demonstrate metastatic disease. Biopsy of the cardiac mass revealed epicarditis without parietal pericardium involvement. Partial gastrectomy was performed to remove the gastric adenocarcinoma.

Conclusion
This is the first reported case of asymptomatic epicarditis. Our case was especially unusual because the epicarditis presented as an incidental cardiac mass. The clinical picture was complicated due to the concomitant presence of gastric adenocarcinoma and chronic pericardial effusion. This case demonstrates that epicarditis should be considered in the differential diagnosis of cardiac masses.
Intraoperative anaphylaxis due to gelofusine in a patient undergoing intramedullary nailing of the femur: a case report
Authors: Polyzois Ioannis , Lampard Andrina , Mohanlal Paras , Tsiridis Evgenios , Manidakis Nikolaos , Tsiridis Eleftherios 
Published: January 2009

Abstract

Background
Although uncommon, anaphylaxis due to a colloid plasma expander can occur peri-operatively

Case presentation
We present a case of an intra-operative cardiac arrest in a 72 year old Caucasian male patient who underwent prophylactic intramedullary nailing for a proximal femoral metastasis from prostate cancer. The patient was resuscitated successfully and the procedure was completed uneventfully. Elevated serum tryptase levels confirmed the diagnosis of an anaphylactic reaction and positive allergy skin prick testing identified gelofusine as the causative agent.

Conclusion
A high index of suspicion, prompt diagnosis and rapid institution of treatment are essential for a safe outcome following such reactions. To our knowledge, this is the first published report of such a severe reaction to gelofusine infusion that occurs during an orthopaedic procedure.
Gastric outlet obstruction possibly secondary to ulceration in a 2-year-old girl: a case report
Authors: Okawada Manabu , Okazaki Tadaharu , Takahashi Tsubasa , Lane Geoffrey J , Yamataka Atsuyuki 
Published: January 2009

Abstract
Gastric outlet obstruction due to ulceration is extremely rare in childhood. We report a case of gastric outlet obstruction possibly secondary to peptic ulceration and our surgical management. Our approach, without vagotomy or antrectomy, would appear to be a safe and effective.
CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines
Authors: Zabouo Gwladys , Imbert Anne-Marie , Jacquemier Jocelyne , Finetti Pascal , Moreau Thomas , Esterni Benjamin , Birnbaum Daniel , Bertucci François , Chabannon Christian 
Published: January 2009

Abstract
Introduction
Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell–cell and cell–matrix interactions. CD146 (MCAM) is associated with an advanced tumor stage in melanoma, prostate cancer and ovarian cancer. Studies of CD146 expression and function in breast cancer remain scarce except for a report concluding that CD146 could act as a tumor suppressor in breast carcinogenesis.

Methods
To resolve these apparent discrepancies in the role of CD146 in tumor cells, we looked at the association of CD146 expression with histoclinical features in human primary breast cancers using DNA and tissue microarrays. By flow cytometry, we characterized CD146 expression on different breast cancer cell lines. Using siRNA or shRNA technology, we studied functional consequences of CD146 downmodulation of MDA-MB-231 cells in migration assays. Wild-type, mock-transfected and downmodulated transfected cells were profiled using whole-genome DNA microarrays to identify genes whose expression was modified by CD146 downregulation.

Results
Microarray studies revealed the association of higher levels of CD146 with histoclinical features that belong to the basal cluster of human tumors. Expression of CD146 protein on epithelial cells was detected in a small subset of cancers with histoclinical features of basal tumors. CD146+ cell lines displayed a mesenchymal phenotype. Downmodulation of CD146 expression in the MDA-MB-231 cell line resulted in downmodulation of vimentin, as well as of a set of genes that include both genes associated with a poor prognosis in a variety of cancers and genes known to promote cell motility. In vitro functional assays revealed decreased migration abilities associated with decreased CD146 expression.

Conclusions
In addition to its expression in the vascular compartment, CD146 is expressed on a subset of epithelial cells in malignant breast. CD146 may directly or indirectly contribute to tumor aggressiveness by promoting malignant cell motility. Changes in molecular signatures following downmodulation of CD146 expression suggest that CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process.
Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes
Authors: Balasubramanian Suganthi , Zheng Deyou , Liu Yuen-Jong , Fang Gang , Frankish Adam , Carriero Nicholas , Robilotto Rebecca , Cayting Philip , Gerstein Mark 
Published: January 2009

Abstract
Background
The availability of genome sequences of numerous organisms allows comparative study of pseudogenes in syntenic regions. Conservation of pseudogenes suggests that they might have a functional role in some instances.

Results
We report the first large-scale comparative analysis of ribosomal protein pseudogenes in four mammalian genomes (human, chimpanzee, mouse and rat). To this end, we have assigned these pseudogenes in the four organisms using an automated pipeline and make the results available online. Each organism has a large number of ribosomal protein pseudogenes (approximately 1,400 to 2,800). The majority of them are processed (generated by retrotransposition). However, we do not see a correlation between the number of pseudogenes associated with a ribosomal protein gene and its mRNA abundance. Analysis of pseudogenes in syntenic regions between species shows that most are conserved between human and chimpanzee, but very few are conserved between primates and rodents. Interestingly, syntenic pseudogenes have a lower rate of nucleotide substitution than their surrounding intergenic DNA. Moreover, evidence from expressed sequence tags indicates that two pseudogenes conserved between human and mouse are transcribed. Detailed analysis shows that one of them, the pseudogene of RPS27, is likely to be a protein-coding gene. This is significant as previous reports indicated there are exactly 80 ribosomal protein genes encoded by the human genome.

Conclusions
Our analysis indicates that processed ribosomal protein pseudogenes abound in mammalian genomes, but few of these are conserved between primates and rodents. This highlights the large amount of recent retrotranspositional activity in mammals and a relatively larger amount of it in the rodent lineage.
Localized Genetic Structure Persists in Wild Populations of Chinook Salmon in the John Day River Despite Gene Flow from Outside Sources
Authors: Narum Shawn R. , Schultz Terra L. , Van Doornik Donald M. , Teel David 
Published: January 2009

AbstractSamples of Chinook salmon Oncorhynchus tshawytscha collected from four spawning areas in the John Day River, Oregon (n = 330), were genotyped with 13 microsatellite loci to test for bottlenecks and temporal stability within sites as well as genetic differentiation among sites, and to estimate gene flow from outside populations. Since the John Day River has never been stocked with hatchery‐reared fish, this study provided the opportunity to evaluate the genetic integrity and structure of Chinook salmon in a wilderness area amid many hatchery‐supported populations in the Columbia River. No tests for bottlenecks (Wilcoxon tests for heterozygosity excess) were significant, and the temporal variation was slight and not significant within any spawning reach except for the collections from the Middle Fork John Day River. Overall, the genetic distance estimates suggest that there are three distinct subpopulations in the John Day River, namely, those in (1) the North Fork John Day River (including Granite Creek), (2) the Middle Fork John Day River, and (3) the upper main‐stem John Day River. These genetic relationships were supported by results from a neighbor‐joining dendrogram. Assignment tests indicate that out‐of‐basin straying occurs throughout the John Day River, the largest percentage of strays going to the North Fork John Day River. Immigration may have acted to avert genetic bottlenecks and maintain genetic diversity in populations with fluctuating census size. Yet the genetic substructure of the Chinook salmon in the John Day River indicates natural reproduction from philopatric individuals, possibly with higher reproductive success than immigrants. The evidence presented here elucidates the balance of philopatry and dispersal acting to maintain genetic diversity and localized structure among the Chinook salmon of the John Day River.
Does Adhesive Thickness Affect Resin-dentin Bond Strength After Thermal/Load Cycling?
Authors: Lodovici E. , Reis A. , Geraldeli S. , Ferracane J. L. , Ballester R. Y. , Filho L. E. R. 
Published: January 2009

Clinical Relevance
The application of an extra coat of hydrophobic, solvent-free bonding resin, designed to act as an intermediate flexible layer, was not able to minimize the damage caused by thermal/mechanical load cycling in low C-factor cavities.
Influence of Oversized Dowel Space Preparation on the Bond Strengths of FRC Posts
Authors: Schmage P. , Pfeiffer P. , Pinto E. , Platzer U. , Nergiz I. 
Published: January 2009

Clinical Relevance
Build-up composites could not fulfil the expectations to bond an FRC post into wide dowel spaces with the same bond strength as a precisely fitting FRC post.