bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of the biochemical modifications caused by toxic and non‐toxic protein oligomers in cells
Authors: Zampagni Mariagioia , Cascella Roberta , Casamenti Fiorella , Grossi Cristina , Evangelisti Elisa , Wright Daniel , Becatti Matteo , Liguri Gianfranco , Mannini Benedetta , Campioni Silvia , Chiti Fabrizio , Cecchi Cristina 
Published: December 2010

AbstractPeptides and proteins can convert from their soluble forms into highly ordered fibrillar aggregates, giving rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. It is increasingly recognized that protein oligomers forming early in the process of fibril aggregation represent the pathogenic species in protein deposition diseases. The N‐terminal domain of the HypF protein from Escherichia coli (HypF‐N) has previously been shown to form, under distinct conditions, two types of HypF‐N oligomers with indistinguishable morphologies but distinct structural features at the molecular level. Only the oligomer type exposing hydrophobic surfaces and possessing sufficient structural plasticity is toxic (type A), whereas the other type is benign to cultured cells (type B). Here we show that only type A oligomers are able to induce a Ca2+ influx from the cell medium to the cytosol, to penetrate the plasma membrane, to increase intracellular reactive oxygen species production, lipid peroxidation and release of intracellular calcein, resulting in the activation of the apoptotic pathway. Remarkably, these oligomers can also induce a loss of cholinergic neurons when injected into rat brains. By contrast, markers of cellular stress and viability were unaffected in cultured and rat neuronal cells exposed to type B oligomers. The analysis of the time scales of such effects indicates that the difference of toxicity between the two oligomer types involve the early events of the toxicity cascade, shedding new light on the mechanism of action of protein oligomers and on the molecular targets for the therapeutic intervention against protein deposition diseases.
Therapeutic effects of human STRO‐3‐selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia
Authors: See Fiona , Seki Tetsunori , Psaltis Peter J. , Sondermeijer Hugo P. , Gronthos Stan , Zannettino Andrew C.W. , Govaert Klaas M. , Schuster Michael D. , Kurlansky Paul A. , Kelly Darren J. , Krum Henry , Itescu Silviu 
Published: December 2010

AbstractStromal precursor antigen (STRO)‐3 has previously been shown to identify a subset of adult human bone marrow (BM)‐derived mesenchymal lineage precursors, which may have cardioprotective potential. We sought to characterize STRO‐3‐immunoselected and culture‐expanded mesenchymal precursor cells (MPCs) with respect to their biology and therapeutic potential in myocardial ischemia. Immunoselection of STRO‐3+ MPCs enriched for fibroblastic colony forming units from unfractionated BM mononuclear cells (MNCs). Compared to mesenchymal stem cells conventionally isolated by plastic adherence, MPCs demonstrated increased proliferative capacity during culture expansion, expressed higher levels of early ‘stem cell’ markers and various pro‐angiogenic and cardioprotective cytokines, and exhibited greater trilineage developmental efficiency. Intramyocardial injection of MPCs into a rat model of myocardial infarction (MI) promoted left ventricular recovery and inhibited left ventricular dilatation. These beneficial effects were associated with cardioprotective and pro‐angiogenic effects at the tissue level, despite poor engraftment of cells. Treatment of MI rats with MPC‐conditioned medium (CM) preserved left ventricular function and dimensions, reduced myocyte apoptosis and fibrosis, and augmented neovascularization, involving both resident vascular cells and circulating endothelial progenitor cells (EPCs). Profiling of CM revealed various cardioprotective and pro‐angiogenic factors, which had biological activity in cultures of myocytes, tissue‐resident vascular cells and EPCs. Prospective immunoselection of STRO‐3+ MPCs from BM MNCs conferred advantage in maintaining a population of immature MPCs during ex vivo expansion. Transplantation of culture‐expanded MPCs into the post‐MI heart resulted in therapeutic benefit, attributable at least in part to paracrine mechanisms of action. Thus, MPCs represent a promising therapy for myocardial ischemia.
Going beyond the author: what retellings tell us about comprehending narrative and expository texts
Authors: Kucer Stephen B. 
Published: December 2010

AbstractThis research examines the nature of comprehended meanings that do not match those of the author. These meanings were generated by two groups of fourth graders after reading a narrative or expository text. Readers read their respective texts aloud, followed by a recall and probes. Reading behaviours were examined to establish that processing difficulties did not significantly impact reader comprehension. Retold clauses that did not match those in the text were classified using a retelling taxonomy: substitution, addition, summary, conflict, rearrangement, omission. It was discovered that both groups of readers went beyond the information given, approximately 18 per cent of the time for the narration and 59 per cent of the time for the exposition. Additionally, the profiles of this information varied between the two groups. Narrative retellings contained a high percentage of conflicts, with very few substitutions, summaries or rearrangement of ideas. In contrast, expository retellings had significant numbers of substitutions and summaries, with fewer additions and rearrangements. It is hypothesised that reader background knowledge accounted for the variation in the retelling profiles and that this background facilitated as well as inhibited understanding. Given such variation even among these proficient readers, teachers not only need to help students develop background knowledge related to the text, but also encourage readers to cross‐check their understandings with the text. Interestingly, this cross‐checking is especially needed when there is an alignment between reader background and text content.
Perspectives of Iranian male nursing students regarding the role of nursing education in developing a professional identity: A content analysis study
Authors: VAISMORADI Mojtaba , SALSALI Mahvash , AHMADI Fazlollah 
Published: December 2010

AbstractAim:  The purpose of the present study was to explore the perspectives of Iranian male nursing students regarding the role of nursing education in developing a professional identity.Methods:  A qualitative design, based on the content analysis approach, was used to collect the data and analyze the perspectives of 14 Iranian male nursing students who were chosen by using a purposive sampling strategy. After the selection of the participants, semistructured interviews were held in order to collect the data.Results:  During the data analysis, three main themes emerged: “reality–expectation incompatibility”, “being supported by the educational system”, and “nursing image rectification”. The second theme consisted of two categories: “feeling trusted” and “being defended”.Conclusions:  This study will be useful to nurse educators and administrators in relation to what constitutes nursing students' professional identity within the Iranian culture and context and how nursing education can play an effective role in developing their professional identity in order to devise strategies to attract male students to the nursing profession and promote their retention after graduation.
The Association Between Erectile Dysfunction and Depressive Symptoms in Men Treated for Prostate Cancer
Authors: Nelson Christian J. , Mulhall John P. , Roth Andrew J. 
Published: December 2010

ABSTRACT

Introduction
The relationship between erectile dysfunction (ED) and depressive symptoms is well established. However, this relationship is not well explored in men with prostate cancer. Limited data suggest men with prostate cancer may experience less ED bother than men with ED who do not have prostate cancer, implying that ED and depressive symptoms may not be associated in men with prostate cancer.

Aim
To determine if ED is associated with depressive symptoms in men with prostate cancer.

Main Outcome Measures
Assessments of quality-of-life (The Functional Assessment of Cancer Therapy [FACT-P]), anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and erectile function. Erectile function was measured with one question from the FACT-P similar to that used by the Massachusetts Male Aging Study.

Methods
Men with prostate cancer, and naïve of hormone treatment, completed the study questionnaires at a single time point.

Results
The average age of the 339 men was 67 ± 10 years. The average time since diagnosis was 3.9 ± 3 years. When answering the question, “I am able to have and maintain an erection” on a 1 to 5 scale (5 representing the best function), the mean score was 2 indicating “a little bit.” On univariate analysis, erectile function and depression were associated, r = −0.12, P &lt; 0.05. Other variables associated with depression were marital status, r = 0.11, P &lt; 0.05; anxiety scores, r = 0.56, P &lt; 0.01; and social support, r = −0.42, P &lt; 0.01. On multivariate analysis, erectile function remained a significant predictor of depression, beta = −0.10, P &lt; 0.05.

Conclusions
Erectile function was associated with depressive symptoms in both univariate and multivariate analysis, indicating that ED is independently associated with depressive symptoms even though patients were approximately 4 years post diagnosis. These cross-sectional data suggest ED in men with prostate cancer can have lasting psychological effects.
The Noradrenergic Action in Antidepressant Treatments: Pharmacological and Clinical Aspects
Authors: Dell’Osso Bernardo , Palazzo M. Carlotta , Oldani Lucio , Altamura A. Carlo 
Published: December 2010

SUMMARYEven though noradrenaline has been recognized as one of the key neurotransmitters in the pathophysiology of major depression (MD), noradrenergic compounds have been less extensively utilized in clinical practice, compared to selective serotonin reuptake inhibitors (SSRIs). The development of the first selective noradrenergic reuptake inhibitor (NRI), Reboxetine, has not substantially changed the state of the art. In addition, Atomoxetine, a relatively pure NRI used for the treatment of ADHD, has shown mixed results when administered in augmentation to depressed subjects. Through a Medline search from 2000 to 2010, the present article provides an updated overview of the main pharmacological and clinical aspects of antidepressant classes that, partially or selectively, act on the noradrenergic systems. The noradrenergic action plays an important clinical effect in different antidepressant classes, as confirmed by the efficacy of dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) Bupropion, and other compounds (e.g., Mianserin, Mirtazapine), which enhance the noradrenergic transmission. In addition, many tricyclics, such as Desipramine and Nortriptyline, have prevalent noradrenergic effect. Monoamine oxidase inhibitors (MAOIs), moreover, block the breakdown of serotonin, noradrenaline, dopamine and increase the availability of these monoamines. A novel class of antidepressants—the triple reuptake inhibitors—is under development to selectively act on serotonin, noradrenaline, and dopamine. Finally, the antidepressant effect of the atypical antipsychotic Quetiapine, indicated for the treatment of bipolar depression, is likely to be related to the noradrenergic action of its metabolite Norquetiapine. Even though a pure noradrenergic action might not be sufficient to obtain a full antidepressant effect, a pronoradrenergic action represents an important element for increasing the efficacy of mixed action antidepressants. In particular, the noradrenergic action seemed to be related to the motor activity, attention, and arousal.
Peritoneal Dialysis in Cats with Acute Kidney Injury: 22 Cases (2001–2006)
Authors: Cooper R.L. , Labato M.A. 
Published: December 2010

Background: Peritoneal dialysis (PD) has been described for use in animals with acute kidney injury refractory to fluid therapy. However, no study has examined the use of PD in a large group of cats.Hypothesis: PD is an important adjunctive therapy to treat acute kidney injury in cats.Animals: The medical records of 22 cats with acute kidney injury that had received PD were examined. Animals were excluded if acute uremia was a result of postrenal causes such as uroabdomen or urethral obstruction.Methods: Medical records were reviewed for the following: indication for PD, outcome, number of cycles performed, survival time, and predialysis and postdialysis results for blood urea nitrogen (BUN), creatinine, potassium, chloride, sodium, phosphorus, total protein, and albumin concentrations, and urine output.Results:Indications for PD include acute‐on‐chronic kidney injury, acute kidney injury caused by toxins, bilateral ureteroliths, bilateral ureteral ligation as a complication of ovariohysterectomy, and unknown causes. The median survival time for all cats on PD was 4 days, although the median survival time for the cats that were discharged was 774 days. The most common complications were dialysate retention and sequestration of dialysate SC. There was a significant (P< .05) decrease between predialysis and postdialysis results for BUN, creatinine, potassium, phosphorus, total protein, and albumin concentrations. There was a significant (P< .05) difference in survival times between sexes.Conclusions and Clinical Importance: PD is an effective option for treatment of cats with acute kidney injury refractory to fluid therapy.
Pharmacodynamic assessment of vancomycin–rifampicin combination against methicillin resistant Staphylococcus aureus biofilm: a parametric response surface analysis
Authors: Salem Ahmed H , Elkhatib Walid F , Noreddin Ayman M 
Published: December 2010

Abstract

Objectives
A combination of vancomycin and rifampicin (rifampin) is commonly used to treat staphylococcal infections but its efficacy against methicillin-resistant Staphylococcus aureus (MRSA) biofilm is controversial. The objective of this study was to use a recently developed quantitative methodology to characterise the killing effect of vancomycin and rifampin combination against MRSA biofilm.

Methods
MRSA biofilm was exposed to escalating concentrations of vancomycin and rifampin and the viability of the biofilm-ensconced bacteria was evaluated. ADAPT II was used to model the concentration–effect relationship and determine the optimal sampling concentrations. Combination experiments were then conducted and the observations were compared with a simulated response surface representing null interaction. Finally, the pharmacodynamic interaction index (PDI) was computed as the ratio of the volumes under the observed and simulated surfaces.

Key findings
In the combination experiments, all observations showed an inferior antibacterial effect to what is expected under null interaction assumption and the PDI was estimated to be 3.36 (95% CI, 3.25 to 3.46).

Conclusions
The results of the study demonstrate in-vitro antagonism between vancomycin and rifampin against MRSA biofilm. The quantitative approach employed to quantify the antibacterial effect of the combination provides a scientific rationale for further in-vivo investigations that should allow a better understanding of the therapeutic potential of this combination in biofilm-associated MRSA infections.
Auranofin Protects against Anthrax Lethal Toxin-Induced Activation of the Nlrp1b Inflammasome
Authors: Newman Zachary L. , Sirianni Nicole , Mawhinney Christina , Lee Margaret S. , Leppla Stephen H. , Moayeri Mahtab , Johansen Lisa M. 
Published: December 2010

ABSTRACTAnthrax lethal toxin (LT) is the major virulence factor forBacillus anthracis. The lethal factor (LF) component of this bipartite toxin is a protease which, when transported into the cellular cytoplasm, cleaves mitogen-activated protein kinase kinase (MEK) family proteins and induces rapid toxicity in mouse macrophages through activation of the Nlrp1b inflammasome. A high-throughput screen was performed to identify synergistic LT-inhibitory drug combinations from within a library of approved drugs and molecular probes. From this screen we discovered that auranofin, an organogold compound with anti-inflammatory activity, strongly inhibited LT-mediated toxicity in mouse macrophages. Auranofin did not inhibit toxin transport into cells or MEK cleavage but inhibited both LT-mediated caspase-1 activation and caspase-1 catalytic activity. Thus, auranofin inhibited LT-mediated toxicity by preventing activation of the Nlrp1b inflammasome and the downstream actions that occur in response to the toxin. Idebenone, an analog of coenzyme Q, synergized with auranofin to increase its protective effect. We found that idebenone functions as an inhibitor of voltage-gated potassium channels and thus likely mediates synergy through inhibition of the potassium fluxes which have been shown to be required for Nlrp1b inflammasome activation.
Diversity of Clavulanic Acid-Inhibited Extended-Spectrum β-Lactamases inAeromonasspp. from the Seine River, Paris, France
Authors: Girlich Delphine , Poirel Laurent , Nordmann Patrice 
Published: December 2010

ABSTRACTEnvironmentalAeromonassp. isolates resistant to ceftazidime were recovered during an environmental survey performed with water samples from the Seine River, in Paris, France, in November 2009. Selected isolates were identified by sequencing of the 16S rRNA andrpoBgenes. PCR and cloning experiments were used to identify broad-spectrum-β-lactamase-encoding genes and their genetic context. Clavulanic acid-inhibited extended-spectrum-β-lactamase (ESBL) genes were identified in 71% of theAeromonassp. isolates. A variety of ESBL genes were detected, includingblaVEB-1a,blaSHV-12,blaPER-1,blaPER-6,blaTLA-2, andblaGES-7, suggesting an aquatic reservoir of those ESBL genes. Moreover, the repeated elements and different insertion sequences were identified in association with theblaPER-6and theblaVEB-1agenes, respectively, indicating a wide diversity of mobilization events, makingAeromonasspp. a vehicle for ESBL dissemination.
Investigation of the Potential for Mutational Resistance to XF-73, Retapamulin, Mupirocin, Fusidic Acid, Daptomycin, and Vancomycin in Methicillin-Resistant
Staphylococcus aureus
Isolates during a 55-Passage Study
Authors: Farrell David J. , Robbins Marion , Rhys-Williams William , Love William G. 
Published: December 2010

ABSTRACT

XF-73 is a dicationic porphyrin drug with rapid Gram-positive antibacterial activity currently undergoing clinical trials for the nasal decolonization of
Staphylococcus aureus
, including methicillin-resistant
Staphylococcus aureus
(MRSA). In multistep (55-passage) resistance selection studies in the presence of subinhibitory concentrations of XF-73, retapamulin, mupirocin, fusidic acid, and vancomycin against four Network on Antimicrobial Resistance in
Staphylococcus aureus
MRSA strains, there was no >4-fold increase in the MIC for XF-73 after 55 passages. In contrast, there was an increase in the MICs for retapamulin (from 0.25 μg/ml to 4 to 8 μg/ml), for mupirocin (from 0.12 μg/ml to 16 to 512 μg/ml), for fusidic acid (from 0.12 μg/ml to 256 μg/ml), and for vancomycin (from 1 μg/ml to 8 μg/ml in two of the four strains tested). Further investigations using
S. aureus
NRS384 (USA300) and daptomycin demonstrated a 64-fold increase in the MIC after 55 passages (from 0.5 μg/ml to 32 μg/ml) with a >4-fold increase in the MIC obtained after only five passages. Sequencing analysis of selected isolates confirmed previously reported point mutations associated with daptomycin resistance. No cross-resistance to XF-73 was observed with the daptomycin-resistant strains, suggesting that whereas the two drugs act on the bacterial cell membrane, their specific site of action differs. XF-73 thus represents the first in a new class of antibacterial drugs, which (unlike the comparator antibiotics) after 55 passages exhibited a ≤4-fold increase in MIC against the strains tested. Antibacterial drugs with a low propensity for inducing bacterial resistance are much needed for the prevention and treatment of multidrug-resistant bacteria both within and outside the hospital setting.
Biochemical and Structural Characterization of the Subclass B1 Metallo-β-Lactamase VIM-4
Authors: Lassaux Patricia , Traoré Daouda A. K. , Loisel Elodie , Favier Adrien , Docquier Jean-Denis , Sohier Jean Sébastien , Laurent Clémentine , Bebrone Carine , Frère Jean-Marie , Ferrer Jean-Luc , Galleni Moreno 
Published: December 2010

ABSTRACT

The metallo-β-lactamase VIM-4, mainly found in
Pseudomonas aeruginosa
or
Acinetobacter baumannii
, was produced in
Escherichia coli
and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn
2+
at concentrations ranging from 0.4 to 100 μM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 Å. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn
2+
ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.
Contribution of the Rgg Transcription Regulator to Metabolism and Virulence ofStreptococcus suisSerotype 2
Authors: Zheng Feng , Ji Hongfeng , Cao Min , Wang Changjun , Feng Youjun , Li Ming , Pan Xiuzhen , Wang Jing , Qin Yuehong , Hu Fuquan , Tang Jiaqi 
Published: December 2010

ABSTRACTThe Rgg-like regulators, a family of transcription factors commonly found in many Gram-positive bacteria, play multiple roles, especially in the control of pathogen virulence. Here, we report anrgghomologue from a Chinese isolate, 05ZYH33, ofStreptococcus suisserotype 2 (SS2). Deletion of thergggene in SS2 increased its adhesion to Hep-2 cells and hemolytic activityin vitro. Significantly, inactivation of thergggene attenuated SS2 virulence in an experimental piglet infection model. Using DNA microarrays and quantitative reverse transcription-PCR, we found that the Rgg regulator affects the transcriptional profile of 15.87% (n= 345) of all of the annotated chromosomal genes, including those involved in nonglucose carbohydrate metabolism, DNA recombination, protein biosynthesis, bacterial defense mechanisms, and others. It was experimentally verified that the deletion ofrggin SS2 reduced the utilization of nonglucose carbohydrates, such as lactose and maltose. In addition, thergggene was found to be associated with changes in the bacterial microscopic phenotype and growth curve. These data suggested that Rgg in SS2 is a global transcriptional regulator that plays an important role in promoting SS2 bacterial survival during pathogen-host interaction.