bluuebunny/crossref_metadata_2025_split huggingface dataset:
GeBP/GPL Transcription Factors Regulate a Subset ofCPR5-Dependent Processes
Authors: Perazza Daniel , Laporte Frédéric , Balagué Claudine , Chevalier Florian , Remo Shanterika , Bourge Mickaël , Larkin John , Herzog Michel , Vachon Gilles 
Published: August 2011

AbstractThe CONSTITUTIVE EXPRESSOR OF PATHOGENESIS-RELATED GENES5 (CPR5) gene of Arabidopsis (Arabidopsis thaliana) encodes a putative membrane protein of unknown biochemical function and displays highly pleiotropic functions, particularly in pathogen responses, cell proliferation, cell expansion, and cell death. Here, we demonstrate a link between CPR5 and the GLABRA1 ENHANCER BINDING PROTEIN (GeBP) family of transcription factors. We investigated the primary role of the GeBP/GeBP-like (GPL) genes using transcriptomic analysis of the quadruple gebp gpl1,2,3 mutant and one overexpressing line that displays several cpr5-like phenotypes including dwarfism, spontaneous necrotic lesions, and increased pathogen resistance. We found that GeBP/GPLs regulate a set of genes that represents a subset of the CPR5 pathway. This subset includes genes involved in response to stress as well as cell wall metabolism. Analysis of the quintuple gebp gpl1,2,3 cpr5 mutant indicates that GeBP/GPLs are involved in the control of cell expansion in a CPR5-dependent manner but not in the control of cell proliferation. In addition, to our knowledge, we provide the first evidence that the CPR5 protein is localized in the nucleus of plant cells and that a truncated version of the protein with no transmembrane domain can trigger cpr5-like processes when fused to the VP16 constitutive transcriptional activation domain. Our results provide clues on how CPR5 and GeBP/GPLs play opposite roles in the control of cell expansion and suggest that the CPR5 protein is involved in transcription.
Searching for small simple automorphic loops
Authors: Johnson Kenneth W. , Kinyon Michael K. , Nagy Gábor P. , Vojtěchovský Petr 
Published: August 2011

AbstractA loop is (right) automorphic if all its (right) inner mappings are automorphisms. Using the classification of primitive groups of small degrees, we show that there is no non-associative simple commutative automorphic loop of order less than 212, and no non-associative simple automorphic loop of order less than 2500. We obtain numerous examples of non-associative simple right automorphic loops. We also prove that every automorphic loop has the antiautomorphic inverse property, and that a right automorphic loop is automorphic if and only if its conjugations are automorphisms.
Families of explicitly isogenous Jacobians of variable-separated curves
Authors: Smith Benjamin 
Published: August 2011

AbstractWe construct six infinite series of families of pairs of curves (X,Y) of arbitrarily high genus, defined over number fields, together with an explicit isogeny from the Jacobian ofXto the Jacobian ofYsplitting multiplication by 2, 3 or 4. For each family, we compute the isomorphism type of the isogeny kernel and the dimension of the image of the family in the appropriate moduli space. The families are derived from Cassou-Noguès and Couveignes’ explicit classification of pairs (f,g) of polynomials such thatf(x1)−g(x2) is reducible.Supplementary materials are available with this article.
PARETO: A novel evolutionary optimization approach to multiobjective IMRT planning
Authors: Fiege Jason , McCurdy Boyd , Potrebko Peter , Champion Heather , Cull Andrew 
Published: August 2011

Purpose:In radiation therapy treatment planning, the clinical objectives of uniform high dose to the planning target volume (PTV) and low dose to the organs‐at‐risk (OARs) are invariably in conflict, often requiring compromises to be made between them when selecting the best treatment plan for a particular patient. In this work, the authors introduce Pareto‐Aware Radiotherapy Evolutionary Treatment Optimization (pareto), a multiobjective optimization tool to solve for beam angles and fluence patterns in intensity‐modulated radiation therapy (IMRT) treatment planning.Methods:pareto is built around a powerful multiobjective genetic algorithm (GA), which allows us to treat the problem of IMRT treatment plan optimization as a combined monolithic problem, where all beam fluence and angle parameters are treated equally during the optimization. We have employed a simple parameterized beam fluence representation with a realistic dose calculation approach, incorporating patient scatter effects, to demonstrate feasibility of the proposed approach on two phantoms. The first phantom is a simple cylindrical phantom containing a target surrounded by three OARs, while the second phantom is more complex and represents a paraspinal patient.Results:pareto results in a large database of Pareto nondominated solutions that represent the necessary trade‐offs between objectives. The solution quality was examined for several PTV and OAR fitness functions. The combination of a conformity‐based PTV fitness function and a dose‐volume histogram (DVH) or equivalent uniform dose (EUD) ‐based fitness function for the OAR produced relatively uniform and conformal PTV doses, with well‐spaced beams. A penalty function added to the fitness functions eliminates hotspots. Comparison of resulting DVHs to those from treatment plans developed with a single‐objective fluence optimizer (from a commercial treatment planning system) showed good correlation. Results also indicated that pareto shows promise in optimizing the number of beams.Conclusions:This initial evaluation of the evolutionary optimization software toolpareto for IMRT treatment planning demonstrates feasibility and provides motivation for continued development. Advantages of this approach over current commercial methods for treatment planning are many, including: (1) fully automated optimization that avoids human controlled iterative optimization and potentially improves overall process efficiency, (2) formulation of the problem as a true multiobjective one, which provides an optimized set of Pareto nondominated solutions refined over hundreds of generations and compiled from thousands of parameter sets explored during the run, and (3) rapid exploration of the final nondominated set accomplished by a graphical interface used to select the best treatment option for the patient.
Experimental generation of an arbitrarily rotated field‐free line for the use in magnetic particle imaging
Authors: Erbe Marlitt , Knopp Tobias , Sattel Timo F. , Biederer Sven , Buzug Thorsten M. 
Published: August 2011

Purpose:The concept of a magnetic field‐free line (FFL), with regard to the novel tomographic modality magnetic particle imaging (MPI), was recently introduced. Theoretical approaches predict the improvement of sensitivity of MPI by a factor of ten replacing the conventionally used field‐free point (FFP) by a FFL. In this work, an experimental apparatus for generating an arbitrarily rotated and translated FFL field is described and tested.Methods:A theoretical motivation for the implemented setup is provided and the required currents are derived in dependency of the coil sensitivities. A prototype of a FFL field generator is manufactured and the fields are measured using a Hall effect sensor. An evaluation of the generated fields is performed via comparison to simulated data.Results:To utilize the FFL concept for MPI, the setup generating the fields needs to be feasible in praxis with respect to power loss. Furthermore, rotating and translating the FFL, while keeping the setup static in space, is a crucial aspect for conveying FFL imaging to clinical applications. The implemented setup copes with both of these challenges and allows for experimental generation as well as evaluation of the required fields. The generated fields agree to within 3.5% of model predictions.Conclusions:This work transfers the FFL concept from theoretical considerations to the implementation of an experimental setup generating the required fields. The high agreement of the measured fields with simulated data indicates the feasibility of magnetic field generation for the implementation of FFL imaging in MPI.
Clinical Carbapenem-Resistant Acinetobacter baylyi Strain Coharboring
bla
SIM-1
and
bla
OXA-23
from China
Authors: Zhou Zhihui , Du Xiaoxing , Wang Li , Yang Qing , Fu Yiqi , Yu Yunsong 
Published: August 2011

ABSTRACT

bla
SIM-1
and
bla
OXA-23
were codetected in clinical carbapenem-resistant
Acinetobacter baylyi
strain NB09A30. Both of carbapenemase genes were located on a large plasmid (ca. 360 kb).
bla
SIM-1
was found as a gene cassette inserted into a class 1 integron identical to that determined in
Acinetobacter
sp. isolates from South Korea. The genetic structure of
bla
OXA-23
in NB09A30 was different from that in the prevalent
Acinetobacter baumannii
of clonal complex 92 (CC92) from the same hospital.
Biochemical Characterization of Sfh-I, a Subclass B2 Metallo-β-Lactamase from Serratia fonticola UTAD54
Authors: Fonseca Fátima , Arthur Christopher J. , Bromley Elizabeth H. C. , Samyn Bart , Moerman Pablo , Saavedra Maria José , Correia António , Spencer James 
Published: August 2011

ABSTRACT

The subclass B2 metallo-β-lactamase (MBL) Sfh-I from
Serratia fonticola
UTAD54 was cloned and overexpressed in
Escherichia coli
. The recombinant protein binds one equivalent of zinc, as shown by mass spectrometry, and preferentially hydrolyzes carbapenem substrates. However, compared to other B2 MBLs, Sfh-I also shows limited hydrolytic activity against some additional substrates and is not inhibited by a second equivalent of zinc. These data confirm Sfh-I to be a subclass B2 metallo-β-lactamase with some distinctive properties.
Application of Bacterial Bioluminescence To Assess the Efficacy of Fast-Acting Biocides
Authors: Robinson Gareth M. , Tonks Katherine M. , Thorn Robin M. S. , Reynolds Darren M. 
Published: August 2011

ABSTRACTTraditional microbiological techniques are used to provide reliable data on the rate and extent of kill for a range of biocides. However, such techniques provide very limited data regarding the initial rate of kill of fast-acting biocides over very short time domains. This study describes the application of a recombinant strain ofEscherichia coliexpressing thePhotorhabdus luminescens luxoperon as a whole-cell biosensor. Light emission is linked directly to bacterial metabolism; therefore, by monitoring light output, the impact of fast-acting biocides can be assessed. Electrochemically activated solutions (ECASs), bleach, Virkon, and ethanol were assessed at three concentrations (1%, 10%, 80%) in the presence of organic soiling. Over a 2-s time course, 80% ECAS produced the greatest reduction in light output in the absence of organic load but was strongly inhibited by its presence. Eighty percent ethanol outperformed all tested biocides in the presence of organic soil. Bleach and Virkon produced similar reductions in bioluminescence at matched concentrations within the time course of the assay. It was also demonstrated that the assay can be used to rapidly assess the impact of organic soiling. The use of bioluminescent bacteria as whole-cell bioreporters allows assessment of the relative efficacies of fast-acting biocides within milliseconds of application. The assay can be used to investigate activity over short or extended time domains to confirm complete metabolic inhibition of the bioreporter. Moreover, the assay may enable further elucidation of their mechanism of action by allowing the investigation of activity over time domains precluded by traditional microbiology.
Pyrazinoic Acid Decreases the Proton Motive Force, Respiratory ATP Synthesis Activity, and Cellular ATP Levels
Authors: Lu Ping , Haagsma Anna C. , Pham Hoang , Maaskant Janneke J. , Mol Selena , Lill Holger , Bald Dirk 
Published: August 2011

ABSTRACT

Pyrazinoic acid, the active form of the first-line antituberculosis drug pyrazinamide, decreased the proton motive force and respiratory ATP synthesis rates in subcellular mycobacterial membrane assays. Pyrazinoic acid also significantly lowered cellular ATP levels in
Mycobacterium bovis
BCG. These results indicate that the predominant mechanism of killing by this drug may operate by depletion of cellular ATP reserves.
Role of Lipid II and Membrane Thickness in the Mechanism of Action of the Lantibiotic Bovicin HC5
Authors: Paiva Aline Dias , Breukink Eefjan , Mantovani Hilário Cuquetto 
Published: August 2011

ABSTRACT

Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria, nisin being the most well-known member. Nisin inhibits peptidoglycan synthesis and forms pores at sensitive membranes upon interaction with lipid II, the essential bacterial cell wall precursor. Bovicin HC5, a bacteriocin produced by
Streptococcus bovis
HC5, has the putative N-terminal lipid II binding motif, and we investigated the mode of action of bovicin HC5 using both living bacteria and model membranes, with special emphasis on the role of lipid II. Bovicin HC5 showed activity against
Staphylococcus cohnii
and
Staphylococcus warneri
, but bovicin HC5 hardly interfered with the membrane potential of
S. cohnii
. In model membranes, bovicin HC5 was not able to cause carboxyfluorescein release or proton influx from DOPC vesicles containing lipid II. Bovicin HC5 blocked lipid II-dependent pore formation activity of nisin, and a high-affinity interaction with lipid II was observed (apparent binding constant [

K
a

] = 3.1 × 10
6
M
−1
), with a 1:1 stoichiometry. In DOPC vesicles containing lipid II, bovicin HC5 was able to assemble with lipid II into a prepore-like structure. Furthermore, we observed pore formation activity of bovicin HC5, which was stimulated by the presence of lipid II, in thin membranes. Moreover, bovicin HC5 induced the segregation of lipid II into domains in giant model membrane vesicles. In conclusion, bovicin HC5 has a primary mode of action similar to that of nisin, but some differences regarding the pore-forming capacity were demonstrated.
Efficient Identification of Human Immunodeficiency Virus Type 1 Mutants Resistant to a Protease Inhibitor by Using a Random Mutant Library
Authors: Kim Sanggu , Kim Yun-Cheol , Qi Hangfei , Su Kunkai , Morrison Sherie L. , Chow Samson A. 
Published: August 2011

ABSTRACT

Emergence of drug-resistant mutant viruses during the course of antiretroviral therapy is a major hurdle that limits the success of chemotherapeutic treatment to suppress human immunodeficiency virus type 1 (HIV-1) replication and AIDS progression. Development of new drugs and careful patient management based on resistance genotyping data are important for enhancing therapeutic efficacy. However, identifying changes leading to drug resistance can take years of clinical studies, and conventional
in vitro
assays are limited in generating reliable drug resistance data. Here we present an efficient
in vitro
screening assay for selecting drug-resistant variants from a library of randomly mutated HIV-1 strains generated by transposon-directed base-exchange mutagenesis. As a test of principle, we screened a library of mutant HIV-1 strains containing random mutations in the protease gene by using a reporter T-cell line in the presence of the protease inhibitor (PI) nelfinavir (NFV). Analysis of replicating viruses from a single round of infection identified 50 amino acid substitutions at 35 HIV-1 protease residue positions. The selected mutant viruses showed specific resistance to NFV and included most of the known NFV resistance mutations. Therefore, the new assay is efficient for identifying changes leading to drug resistance. The data also provide insights into the molecular mechanisms underlying the development of drug resistance.
Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy
Authors: Takiff Howard , Guerrero Elba 
Published: August 2011

ABSTRACT
While fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.
Impact of Mutations Outside the V3 Region on Coreceptor Tropism Phenotypically Assessed in Patients Infected with HIV-1 Subtype B
Authors: Monno Laura , Saracino Annalisa , Scudeller Luigia , Punzi Grazia , Brindicci Gaetano , Altamura Maurantonio , Lagioia Antonella , Ladisa Nicoletta , Angarano Gioacchino 
Published: August 2011

ABSTRACTHIV coreceptor tropism (CTR) testing is a prerequisite for prescribing a coreceptor antagonist. CTR is increasingly deduced by analyzing the V3 loop sequence of gp120. We investigated the impact of mutations outside V3 on CTR as determined by the enhanced-sensitivity Trofile assay (ESTA). Paired ESTA and gp120 sequencing (population sequencing; from codon 32 of the conserved C1 to the variable V5 domains) were obtained from 60 antiretroviral treatment (ART)-naïve patients (15 with AIDS) infected with subtype B HIV-1. For gp120 sequence analysis, nucleotide mixtures were considered when the second highest electropherogram peak was >25%; sequences were translated into all possible permutations and classified as X4, dual/mixed (DM), and R5 based on coincident ESTA results. ESTA identified R5 and DM viruses in 72 and 28% of patients, respectively; no pure X4 was labeled. Forty percent of AIDS patients had R5 strains. Thirty-two positions, mostly outside V3, were significantly (P< 0.05) different between R5 and DM sequences. According to multivariate analysis, amino acid changes at 9 and 7 positions within the C1 to C4 and V1 to V5 regions, respectively, maintained a statistical significance, as did the net charge of V3 and C4. When analyzing only R5 sequences, 6 positions in the variable regions were found which, along with the V4 net charge, were significantly different for sequences from early- and end-stage disease patients. This study identifies specific amino acid changes outside V3 which contribute to CTR. Extending the analysis to include pure X4 and increasing the sample size would be desirable to define gp120 variables/changes which should be included in predictive algorithms.
Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity against Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula
Authors: Bergen Phillip J. , Forrest Alan , Bulitta Jürgen B. , Tsuji Brian T. , Sidjabat Hanna E. , Paterson David L. , Li Jian , Nation Roger L. 
Published: August 2011

ABSTRACT

The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in
Pseudomonas aeruginosa
. The aim of this study was to systematically investigate
in vitro
bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR)
P. aeruginosa
. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼10
6
and ∼10
8
CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 10
6
-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 10
8
-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 10
6
- and 10
8
-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations.
In Vitro
Activity of Antiretroviral Drugs against Plasmodium falciparum
Authors: Nsanzabana Christian , Rosenthal Philip J. 
Published: August 2011

ABSTRACT

Malaria and HIV infection are both very common in many developing countries. With the increasing availability of therapy for HIV infection, it was of interest to determine whether antiretroviral drugs exert antimalarial effects. We therefore tested the
in vitro
activity of 19 antiretroviral drugs against the W2 and 3D7 strains of
Plasmodium falciparum
at concentrations up to 50 μM. None of 5 tested nucleoside reverse transcriptase inhibitors demonstrated activity. Two nonnucleoside reverse transcriptase inhibitors, efavirenz (mean 50% inhibitory concentration [IC
50
] of 22 to 30 μM against the two strains) and etravirine (3.1 to 3.4 μM), were active; nevirapine was not active. Also active were the fusion inhibitor enfuvirtide (6.2 to 7.9 μM) and the entry inhibitor maraviroc (15 to 21 μM). Raltegravir was not active. However, for all active drugs mentioned above, the IC
50
s were considerably greater than the concentrations achieved with standard dosing. The effects most likely to be clinically relevant were with HIV protease inhibitors. Of the tested compounds, activity was seen with lopinavir (2.7 to 2.9 μM), atazanavir (3.3 to 13.0 μM), saquinavir (5.0 to 12.1 μM), nelfinavir (6.5 to 12.1 μM), ritonavir (9.5 to 10.9 μM), tipranavir (15.5 to 22.3 μM), and amprenavir (28.1 to 40.8) but not darunavir. Lopinavir was active at levels well below those achieved with standard dosing of coformulated lopinavir-ritonavir. Lopinavir also demonstrated modest synergy with the antimalarial lumefantrine (mean fractional inhibitory concentration index of 0.66 for W2 and 0.53 for 3D7). Prior data showed that lopinavir-ritonavir also extends the pharmacokinetic exposure of lumefantrine. Thus, when used to treat HIV infection, lopinavir-ritonavir may have clinically relevant antimalarial activity and also enhance the activity of antimalarials.