bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nationwide Investigation of Extended-Spectrum β-Lactamases, Metallo-β-Lactamases, and Extended-Spectrum Oxacillinases Produced by Ceftazidime-Resistant
Pseudomonas aeruginosa
Strains in France
Authors: Hocquet Didier , Plésiat Patrick , Dehecq Barbara , Mariotte Pierre , Talon Daniel , Bertrand Xavier 
Published: June 2010

ABSTRACT

A nationwide study aimed to identify the extended-spectrum β-lactamases (ESBLs), metallo-β-lactamases (MBLs), and extended-spectrum oxacillinases (ES-OXAs) in a French collection of 140 clinical
Pseudomonas aeruginosa
isolates highly resistant to ceftazidime. Six ESBLs (PER-1,
n
= 3; SHV-2a,
n
= 2; VEB-1a,
n
= 1), four MBLs (VIM-2,
n
= 3; IMP-18,
n
= 1), and five ES-OXAs (OXA-19,
n
= 4; OXA-28,
n
= 1) were identified in 13 isolates (9.3% of the collection). The prevalence of these enzymes is still low in French clinical
P. aeruginosa
isolates but deserves to be closely monitored.
Voriconazole Pharmacokinetics and Safety in Immunocompromised Children Compared to Adult Patients
Authors: Michael Claudia , Bierbach Uta , Frenzel Katrin , Lange Thoralf , Basara Nadezda , Niederwieser Dietger , Mauz-Körholz Christine , Preiss Rainer 
Published: June 2010

ABSTRACT

The aim of this study was to investigate the pharmacokinetics and safety of voriconazole after intravenous (i.v.) administration in immunocompromised children (2 to 11 years old) and adults (20 to 60 years old) who required treatment for the prevention or therapy of systemic fungal infections. Nine pediatric patients were treated with a dose of 7 mg/kg i.v. every 12 h for a period of 10 days. Three children and 12 adults received two loading doses of 6 mg/kg i.v. every 12 h, followed by a maintenance dose of 5 mg/kg (children) or 4 mg/kg (adults) twice a day during the entire study period. Trough voriconazole levels in blood over 10 days of therapy and regular voriconazole levels in blood for up to 12 h postdose on day 3 were examined. Wide intra- and interindividual variations in plasma voriconazole levels were noted in each dose group and were most pronounced in the children receiving the 7-mg/kg dose. Five (56%) of them frequently had trough voriconazole levels in plasma below 1 μg/ml or above 6 μg/ml. The recommended dose of 7 mg/kg i.v. in children provides exposure (area under the concentration-time curve) comparable to that observed in adults receiving 4 mg/kg i.v. The children had significantly higher
C
max
values; other pharmacokinetic parameters were not significantly different from those of adults. Voriconazole exhibits nonlinear pharmacokinetics in the majority of children. Voriconazole therapy was safe and well tolerated in pediatric and adult patients. The European Medicines Agency-approved i.v. dose of 7 mg/kg can be recommended for children aged 2 to <12 years.
Image-Based High-Throughput Drug Screening Targeting the Intracellular Stage of
Trypanosoma cruzi
, the Agent of Chagas' Disease
Authors: Engel Juan C. , Ang Kenny K. H. , Chen Steven , Arkin Michelle R. , McKerrow James H. , Doyle Patricia S. 
Published: June 2010

ABSTRACT

Chagas' disease, caused by infection with the parasite
Trypanosoma cruzi
, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected
T. cruzi
isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells.
T. cruzi
-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4′,6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of
T. cruzi
per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against
T. cruzi
. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.
Immunomodulatory Effects of Serotype B Glucuronoxylomannan from
Cryptococcus gattii
Correlate with Polysaccharide Diameter
Authors: Fonseca Fernanda L. , Nohara Lilian L. , Cordero Radames J. B. , Frases Susana , Casadevall Arturo , Almeida Igor C. , Nimrichter Leonardo , Rodrigues Marcio L. 
Published: June 2010

ABSTRACT

Glucuronoxylomannan (GXM), the major capsular component in the
Cryptococcus
complex, interacts with the immune system in multiple ways, which include the activation of Toll-like receptors (TLRs) and the modulation of nitric oxide (NO) production by phagocytes. In this study, we analyzed several structural parameters of GXM samples from
Cryptococcus neoformans
(serotypes A and D) and
Cryptococcus gattii
(serotypes B and C) and correlated them with the production of NO by phagocytes and the activation of TLRs. GXM fractions were differentially recognized by TLR2/TLR1 (TLR2/1) and TLR2/6 heterodimers expressed on TLR-transfected HEK293A cells. Higher NF-κB luciferase reporter activity induced by GXM was observed in cells expressing TLR2/1 than in cells transfected with TLR2/6 constructs. A serotype B GXM from
C. gattii
was the most effective polysaccharide fraction activating the TLR-mediated response. This serotype B polysaccharide, which was also highly efficient at eliciting the production of NO by macrophages, was similar to the other GXM samples in monosaccharide composition, zeta potential, and electrophoretic mobility. However, immunofluorescence with four different monoclonal antibodies and dynamic light-scattering analysis revealed that the serotype B GXM showed particularities in serological reactivity and had the smallest effective diameter among the GXM samples analyzed in this study. Fractionation of additional serotype B GXMs, followed by exposure of these fractions to macrophages, revealed a correlation between NO production and reduced effective diameters. Our results demonstrate a great functional diversity in GXM samples from different isolates and establish their abilities to differentially activate cellular responses. We propose that serological properties as well as physical chemical parameters, such as the diameter of polysaccharide molecules, may potentially influence the inflammatory response against
Cryptococcus
spp. and may contribute to the differences in granulomatous inflammation between cryptococcal species.
E3 Ubiquitin Ligase Activity and Targeting of BAT3 by MultipleLegionella pneumophilaTranslocated Substrates
Authors: Ensminger Alexander W. , Isberg Ralph R. 
Published: June 2010

ABSTRACTThe intracellular bacterial pathogenLegionella pneumophilamodulates a number of host processes during intracellular growth, including the eukaryotic ubiquitination machinery, which dictates the stability, activity, and/or localization of a large number of proteins. A number ofL. pneumophilaproteins contain eukaryotic-like motifs typically associated with ubiquitination. Central among these is a family of five F-box-domain-containing proteins ofLegionella pneumophila. Each of these five proteins is translocated to the host cytosol by the Dot/Icm type IV protein translocation system during infection. We show that three of these proteins, LegU1, LegAU13, and LicA, interact with components of the host ubiquitination machineryin vivo. In addition, LegU1 and LegAU13 are integrated into functional Skp-Cullin-F-box (SCF) complexes that confer E3 ubiquitin ligase activity. LegU1 specifically interacts with and can direct the ubiquitination of the host chaperone protein BAT3. In a screen for additionalL. pneumophilaproteins that associate with LegU1 in mammalian cells, we identified the bacterial protein Lpg2160. We demonstrate that Lpg2160 also associates with BAT3 independently of LegU1. We show that Lpg2160 is a translocated substrate of the Dot/Icm system and contains a C-terminal translocation signal. We propose a model in which LegU1 and Lpg2160 may function redundantly or in concert to modulate BAT3 activity during the course of infection.
Nitrogen cross-sectional area on standard graphite
Authors: Cascarini de Torre L. E. , Llanos J. L. , Bottani E. J. 
Published: June 2010

Nitrogen physical adsorption at 77.5 and 80.4 K on a standard graphite was studied with the purpose too analyze adsorption models and to determine nitrogen cross-sectional areas for each model. With this intention different models, such as Van der Waals, Langmuir, and BET, which describe the adsorption process at different surface coverages were employed. Molar differential entropies and isosteric heats of adsorption were calculated. A two-dimensional phase transition was confirmed. Adsorbed molecule cross-sectional areas were determined at different surface coverages, by direct comparison with that corresponding to argon. The values obtained varied in a wide range (0.135 to 0.166 nm2) depending on surface coverage.
Effect of Nonuniform Muscle Contraction on Sustainability and Frequency of Triggered Arrhythmias in Rat Cardiac Muscle
Authors: Miura Masahito , Nishio Taichi , Hattori Taiki , Murai Naomi , Stuyvers Bruno D. , Shindoh Chiyohiko , Boyden Penelope A. 
Published: June 2010

Background—Arrhythmias are benign or lethal, depending on their sustainability and frequency. To determine why lethal arrhythmias are prone to occur in diseased hearts, usually characterized by nonuniform muscle contraction, we investigated the effect of nonuniformity on sustainability and frequency of triggered arrhythmias.Methods and Results—Force, membrane potential, and intracellular Ca2+concentration ([Ca2+]i) were measured in 51 rat ventricular trabeculae. Nonuniform contraction was produced by exposing a restricted region of muscle to a jet of 20 mmol/L 2,3-butanedione monoxime (BDM) or 20 μmol/L blebbistatin. Sustained arrhythmias (>10 seconds) could be induced by stimulus trains for 7.5 seconds only with the BDM or blebbistatin jet (100 nmol/L isoproterenol, 1.0 mmol/L [Ca2+]o, 24°C). During sustained arrhythmias, Ca2+surges preceded synchronous increases in [Ca2+]i, whereas the stoppage of the BDM jet made the Ca2+surges unclear and arrested sustained arrhythmias (n=6). With 200 nmol/L isoproterenol, 2.5 mmol/L [Ca2+]o, and the BDM jet, lengthening or shortening of the muscle during sustained arrhythmias accelerated or decelerated their cycle in both the absence (n=10) and presence (n=10) of 100 μmol/L streptomycin, a stretch-activated channel blocker, respectively. The maximum rate of force relaxation correlated inversely with the change in cycle lengths (n=14;P<0.01). Sustained arrhythmias with the BDM jet were significantly accelerated by 30 μmol/L SCH00013, a Ca2+sensitizer of myofilaments (n=10).Conclusion—These results suggest that nonuniformity of muscle contraction is an important determinant of the sustainability and frequency of triggered arrhythmias caused by the surge of Ca2+dissociated from myofilaments in cardiac muscle.
Long-Term Evaluation of the Risk of Recurrence After Cerebral Sinus-Venous Thrombosis
Authors: Martinelli Ida , Bucciarelli Paolo , Passamonti Serena M. , Battaglioli Tullia , Previtali Emanuele , Mannucci Pier Mannuccio 
Published: June 2010

Background—The clinical course of cerebral sinus-venous thrombosis (CSVT) is largely unknown because prospective studies with a long follow-up and with the goal to assess thrombosis recurrence rate and predisposing factors for recurrence are lacking.Methods and Results—One hundred forty-five patients with a first CSVT were followed up for a median of 6 years after discontinuation of anticoagulant treatment. End points were recurrent CSVT or other clinical manifestations of venous thromboembolism. CSVT recurred in 5 patients (3%) and other manifestations of venous thromboembolism (deep vein thrombosis of the lower limbs or pulmonary embolism) were seen in 10 additional patients (7%), for a recurrence rate of 2.03 per 100 person-years (95% confidence interval, 1.16 to 3.14) for all manifestations of venous thromboembolism and 0.53 per 100 person-years (95% confidence interval, 0.16 to 1.10) for CSVT. Nearly half of the recurrences occurred within the first year after discontinuation of anticoagulant therapy. Risk factors for recurrent venous thrombosis were male sex (adjusted hazard ratio, 9.66; 95% confidence interval, 2.86 to 32.7) and, for thromboses other than CSVT, severe thrombophilia resulting from antithrombin, protein C, protein S deficiency, anti-phospholipid antibodies, or combined abnormalities (adjusted hazard ratio, 4.71; 95% confidence interval, 1.34 to 16.5).Conclusions—The risk of recurrent CSVT is low and is higher in the first year after discontinuation of anticoagulant treatment and among men. Mild thrombophilia abnormalities are not associated with recurrent CSVT, but severe thrombophilia entails an increased risk of deep vein thrombosis of the lower limbs or pulmonary embolism.
Examination of the Mixed Layer Deepening Process during Convection Using LES
Authors: Noh Yign , Goh Gahyun , Raasch Siegfried 
Published: June 2010

Abstract
Analysis of large-eddy simulation data of the ocean mixed layer under convection reveals that the contribution from wind stress decreases with time as a result of inertial oscillation in the extratropical ocean and that it leads to a rapid increase of the bulk and gradient Richardson number at the mixed layer depth. The criteria for the mixed layer deepening in the widely used mixed layer models, such as the Niiler–Kraus (NK) model, the Price–Weller–Pinkel (PWP) model, and the K-profile parameterization (KPP) model, are examined in view of these results, and its implication on the model predictability is discussed.
CloudSat as a Global Radar Calibrator
Authors: Protat A. , Bouniol D. , O’Connor E. J. , Klein Baltink H. , Verlinde J. , Widener K. 
Published: June 2010

Abstract
The calibration of the CloudSat spaceborne cloud radar has been thoroughly assessed using very accurate internal link budgets before launch, comparisons with predicted ocean surface backscatter at 94 GHz, direct comparisons with airborne cloud radars, and statistical comparisons with ground-based cloud radars at different locations of the world. It is believed that the calibration of CloudSat is accurate to within 0.5–1 dB. In the present paper it is shown that an approach similar to that used for the statistical comparisons with ground-based radars can now be adopted the other way around to calibrate other ground-based or airborne radars against CloudSat and/or to detect anomalies in long time series of ground-based radar measurements, provided that the calibration of CloudSat is followed up closely (which is the case). The power of using CloudSat as a global radar calibrator is demonstrated using the Atmospheric Radiation Measurement cloud radar data taken at Barrow, Alaska, the cloud radar data from the Cabauw site, Netherlands, and airborne Doppler cloud radar measurements taken along the CloudSat track in the Arctic by the Radar System Airborne (RASTA) cloud radar installed in the French ATR-42 aircraft for the first time. It is found that the Barrow radar data in 2008 are calibrated too high by 9.8 dB, while the Cabauw radar data in 2008 are calibrated too low by 8.0 dB. The calibration of the RASTA airborne cloud radar using direct comparisons with CloudSat agrees well with the expected gains and losses resulting from the change in configuration that required verification of the RASTA calibration.
Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL–positive leukemic cells
Authors: Tanaka Ruriko , Squires Matthew S. , Kimura Shinya , Yokota Asumi , Nagao Rina , Yamauchi Takahiro , Takeuchi Miki , Yao Hisayuki , Reule Matthias , Smyth Tomoko , Lyons John F. , Thompson Neil T. , Ashihara Eishi , Ottmann Oliver G. , Maekawa Taira 
Published: June 2010

AbstractDespite promising clinical results from imatinib mesylate and second-generation ABL tyrosine kinase inhibitors (TKIs) for most BCR-ABL+ leukemia, BCR-ABL harboring the mutation of threonine 315 to isoleucine (BCR-ABL/T315I) is not targeted by any of these agents. We describe the in vitro and in vivo effects of AT9283 (1-cyclopropyl-3[5-morpholin-4yl methyl-1H-benzomidazol-2-yl]-urea), a potent inhibitor of several protein kinases, including Aurora A, Aurora B, Janus kinase 2 (JAK2), JAK3, and ABL on diverse imatinib-resistant BCR-ABL+ cells. AT9283 showed potent antiproliferative activity on cells transformed by wild-type BCR-ABL and BCR-ABL/T315I. AT9283 inhibited proliferation in a panel of BaF3 and human BCR-ABL+ cell lines both sensitive and resistant to imatinib because of a variety of mechanisms. In BCR-ABL+ cells, we confirmed inhibition of substrates of both BCR-ABL (signal transducer and activator of transcription-5) and Aurora B (histone H3) at physiologically achievable concentrations. The in vivo effects of AT9283 were examined in several mouse models engrafted either subcutaneously or intravenously with BaF3/BCR-ABL, human BCR-ABL+ cell lines, or primary patient samples expressing BCR-ABL/T315I or glutamic acid 255 to lysine, another imatinib-resistant mutation. These data together support further clinical investigation of AT9283 in patients with imatinib- and second-generation ABL TKI-resistant BCR-ABL+ cells, including T315I.
Identification of population substructure among Jews using STR markers and dependence on reference populations included
Authors: Listman Jennifer B , Hasin Deborah , Kranzler Henry R , Malison Robert T , Mutirangura Apiwat , Sughondhabirom Atapol , Aharonovich Efrat , Spivak Baruch , Gelernter Joel 
Published: June 2010

AbstractBackgroundDetecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population.ResultsUsing 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses.ConclusionsAlthough clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage.
Expression profiling of Crambe abyssinicaunder arsenate stress identifies genes and gene networks involved in arsenic metabolism and detoxification
Authors: Paulose Bibin , Kandasamy Suganthi , Dhankher Om Parkash 
Published: June 2010

Abstract

Background
Arsenic contamination is widespread throughout the world and this toxic metalloid is known to cause cancers of organs such as liver, kidney, skin, and lung in human. In spite of a recent surge in arsenic related studies, we are still far from a comprehensive understanding of arsenic uptake, detoxification, and sequestration in plants. Crambe abyssinica, commonly known as 'abyssinian mustard', is a non-food, high biomass oil seed crop that is naturally tolerant to heavy metals. Moreover, it accumulates significantly higher levels of arsenic as compared to other species of the Brassicaceae family. Thus, C. abyssinica has great potential to be utilized as an ideal inedible crop for phytoremediation of heavy metals and metalloids. However, the mechanism of arsenic metabolism in higher plants, including C. abyssinica, remains elusive.

Results
To identify the differentially expressed transcripts and the pathways involved in arsenic metabolism and detoxification, C. abyssinica plants were subjected to arsenate stress and a PCR-Select Suppression Subtraction Hybridization (SSH) approach was employed. A total of 105 differentially expressed subtracted cDNAs were sequenced which were found to represent 38 genes. Those genes encode proteins functioning as antioxidants, metal transporters, reductases, enzymes involved in the protein degradation pathway, and several novel uncharacterized proteins. The transcripts corresponding to the subtracted cDNAs showed strong upregulation by arsenate stress as confirmed by the semi-quantitative RT-PCR.

Conclusions
Our study revealed novel insights into the plant defense mechanisms and the regulation of genes and gene networks in response to arsenate toxicity. The differential expression of transcripts encoding glutathione-S-transferases, antioxidants, sulfur metabolism, heat-shock proteins, metal transporters, and enzymes in the ubiquitination pathway of protein degradation as well as several unknown novel proteins serve as molecular evidence for the physiological responses to arsenate stress in plants. Additionally, many of these cDNA clones showing strong upregulation due to arsenate stress could be used as valuable markers. Further characterization of these differentially expressed genes would be useful to develop novel strategies for efficient phytoremediation as well as for engineering arsenic tolerant crops with reduced arsenic translocation to the edible parts of plants.