bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Transcriptional Response of
Bacillus subtilis
to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis
Authors: Lin Janine T. , Connelly Mariah Bindel , Amolo Chris , Otani Suzie , Yaver Debbie S. 
Published: April 2005

ABSTRACT

Global
gene expression patterns of
Bacillus subtilis
in response to
subinhibitory concentrations of protein synthesis inhibitors
(chloramphenicol, erythromycin, and gentamicin) were studied by DNA
microarray analysis.
B. subtilis
cultures were treated with
subinhibitory concentrations of protein synthesis inhibitors for 5, 15,
30, and 60 min, and transcriptional patterns were measured throughout
the time course. Three major classes of genes were affected by the
protein synthesis inhibitors: genes encoding transport/binding
proteins, genes involved in protein synthesis, and genes involved in
the metabolism of carbohydrates and related molecules. Similar
expression patterns for a few classes of genes were observed due to
treatment with chloramphenicol (0.4× MIC) or erythromycin
(0.5× MIC), whereas expression patterns of gentamicin-treated
cells were distinct. Expression of genes involved in metabolism of
amino acids was altered by treatment with chloramphenicol and
erythromycin but not by treatment with gentamicin. Heat shock genes
were induced by gentamicin but repressed by chloramphenicol. Other
genes induced by the protein synthesis inhibitors included the
yheIH
operon encoding ABC transporter-like proteins, with
similarity to multidrug efflux proteins, and the
ysbAB
operon
encoding homologs of LrgAB that function to inhibit cell wall cleavage
(murein hydrolase activity) and convey penicillin tolerance in
Staphylococcus
aureus
.
OXA-46, a New Class D β-Lactamase of Narrow Substrate Specificity Encoded by ablaVIM-1-Containing Integron from aPseudomonas aeruginosaClinical Isolate
Authors: Giuliani Francesco , Docquier Jean-Denis , Riccio Maria Letizia , Pagani Laura , Rossolini Gian Maria 
Published: April 2005

ABSTRACTA novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistantPseudomonas aeruginosaclinical isolate. The variable region of the integron also contained ablaVIM-1metallo-β-lactamase cassette and a duplicatedaacA4aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D β-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates ofBurkholderia cepaciaand in unidentified bacteria from a wastewater plant. Expression ofblaOXA-46inEscherichia colidecreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced inE. coliand purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D β-lactamases.
Benznidazole Therapy inTrypanosoma cruzi-Infected Mice Blocks Thymic Involution and Apoptosis of CD4+CD8+Double-Positive Thymocytes
Authors: Olivieri B. P. , Farias-De-Oliveira D. A. , Araujo-Jorge T. C. , Cotta-de-Almeida V. 
Published: April 2005

ABSTRACTSeveral alterations involving peripheral lymphoid organs have been extensively described after experimentalTrypanosoma cruziinfection. Thymic involution occurs as well in infected mice, with both structural and functional alterations in the organ. Despite these abnormalities, specific immune response proceeds to control parasitemia and the participation of T lymphocytes is essential. However, there are relatively few studies on the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide) upon this response. In this present work, we decided to evaluate the impact of benznidazole treatment upon the thymus involution following acuteT. cruziinfection in mice. We have provided evidence that benznidazole treatment controls the severe abnormalities seen in the thymus due toT. cruziinfection. The thymocyte loss related to the depletion of double-positive CD4+CD8+thymocytes was clearly prevented, corroborating the idea that the mechanism responsible for the prevention of thymus involution is related to the decrease of apoptosis rate in this subset after benznidazole treatment. Furthermore, we demonstrated the prevention of enhanced extracellular matrix deposition in the thymus. In conclusion, the preservation of thymus homeostasis, even though partial, was accomplished after benznidazole treatment. Our data are consistent with the notion that different outcomes ofT. cruziinfection may be linked to differences in the parasite load concomitant to fine tuning of the host immune response.
Lethality of Quinolones against
Mycobacterium smegmatis
in the Presence or Absence of Chloramphenicol
Authors: Malik Muhammad , Lu Tao , Zhao Xilin , Singh Anubha , Hattan Christopher M. , Domagala John , Kerns Robert , Drlica Karl 
Published: April 2005

ABSTRACT

Quinolones were examined for rapid lethal activity against
Mycobacterium smegmatis
in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large C-7 substituents, showed modest bacteriostatic activity. Unlike other quinolones, the dimers failed to display lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not been observed with other bacteria and may therefore reflect unique aspects of mycobacterial gyrase.
Pharmacokinetics of Tenofovir in Breast Milk of Lactating Rhesus Macaques
Authors: Van Rompay Koen K. A. , Hamilton Marta , Kearney Brian , Bischofberger Norbert 
Published: April 2005

ABSTRACT
To study tenofovir transfer into milk, two lactating macaques were given a subcutaneous dose of tenofovir (30 mg/kg of body weight). Peak concentrations and area under the curve values of tenofovir in milk were ∼3 and ∼20% of those detected in serum, respectively.
Identification of a Progenitor of the CTX-M-9 Group of Extended-Spectrum β-Lactamases from
Kluyvera georgiana
Isolated in Guyana
Authors: Olson Adam B. , Silverman M. , Boyd David A. , McGeer Allison , Willey Barbara M. , Pong-Porter V. , Daneman N. , Mulvey Michael R. 
Published: April 2005

ABSTRACT

Chromosomal β-lactamase genes (
bla
KLUY
) from six
Kluyvera georgiana
strains isolated in Guyana were cloned and expressed in
Escherichia coli
. KLUY-1 exhibited 100% amino acid identity with the extended-spectrum β-lactamase CTX-M-14. We also show that a 2.7-kb
Kluyvera
chromosomal region exhibits 99% nucleotide identity to a portion of In60 that includes
bla
CTX-M-9
.
High Genetic Diversity of Ciprofloxacin-Nonsusceptible Isolates of
Streptococcus pneumoniae
in Poland
Authors: Sadowy Ewa , Izdebski Radosław , Skoczyńska Anna , Gniadkowski Marek , Hryniewicz Waleria 
Published: April 2005

ABSTRACT
We have analyzed the susceptibility to ciprofloxacin of 697 pneumococcal isolates collected in 1998-2002 in Poland from patients with respiratory tract diseases. Thirty-one ciprofloxacin-nonsusceptible isolates (MICs, ≥4 μg/ml) were identified, of which two were resistant to levofloxacin (MIC, 8 μg/ml). Serotyping, pulsed-field gel electrophoresis, multilocus sequence typing, and the analysis of resistance determinants showed their great genetic diversity.
Formation of Extreme Cold-Air Pools in Elevated Sinkholes: An Idealized Numerical Process Study
Authors: Zängl Günther 
Published: April 2005

High-resolution numerical simulations with the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) are presented to investigate the processes leading to the formation of extreme cold-air pools in elevated sinkholes. The simulations are idealized in the sense that they are conducted with idealized model topography and with idealized large-scale conditions representing an undisturbed wintertime high pressure situation. After a number of model modifications, the temperature fields, radiative cooling rates, and sensible heat fluxes simulated by the model were in good agreement with the available observations, giving confidence that the model is suitable for this process study. The model results indicate a number of necessary preconditions for the formation of an extreme cold-air pool in a sinkhole. Apart from undisturbed clear weather, a small heat conductivity of the ground and an effective mechanism drying the low-level air during the cooling process are required. The importance of the heat conductivity results from the fact that the net cooling of the ground is only a small residual between the net radiative heat loss and the ground heat flux. As a consequence, extreme cooling events are strongly favored by the presence of freshly fallen powder snow. The necessity of a drying mechanism is related to the strong temperature dependence of the saturation vapor pressure, decreasing by a factor of about 2.5 per 10 K temperature decrease at temperatures below −20°C. Except in cases of very dry ambient air, a nocturnal cooling by 25 or 30 K (as observed in extreme cases) must be accompanied by an order-of-magnitude reduction of the water vapor mixing ratio to prevent the formation of fog. According to the simulations, the most effective drying mechanism is provided by the formation of ice clouds and the subsequent sedimentation of the ice particles. Near the surface, direct deposition of water vapor at the ground also seems to play a significant role.
Using Probability Density Functions to Derive Consistent Closure Relationships among Higher-Order Moments
Authors: Larson Vincent E. , Golaz Jean-Christophe 
Published: April 2005

Parameterizations of turbulence often predict several lower-order moments and make closure assumptions for higher-order moments. In principle, the low- and high-order moments share the same probability density function (PDF). One closure assumption, then, is the shape of this family of PDFs. When the higher-order moments involve both velocity and thermodynamic scalars, often the PDF shape has been assumed to be a double or triple delta function. This is equivalent to assuming a mass-flux model with no subplume variability. However, PDF families other than delta functions can be assumed. This is because the assumed PDF methodology is fairly general. This paper proposes closures for several third- and fourth-order moments. To derive the closures, the moments are assumed to be consistent with a particular PDF family, namely, a mixture of two trivariate Gaussians. (This PDF is also called a double Gaussian or binormal PDF by some authors.) Separately from the PDF assumption, the paper also proposes a simplified relationship between scalar and velocity skewnesses. This PDF family and skewness relationship are simple enough to yield simple, analytic closure formulas relating the moments. If certain conditions hold, this set of moments is specifically realizable. By this it is meant that the set of moments corresponds to a real Gaussian-mixture PDF, one that is normalized and nonnegative everywhere. This paper compares the new closure formulas with both large eddy simulations (LESs) and closures based on double and triple delta PDFs. This paper does not implement the closures in a single-column model and test them interactively. Rather, the comparisons are diagnostic; that is, low-order moments are extracted from the LES and treated as givens that are input into the closures. This isolates errors in the closures from errors in a single-column model. The test cases are three atmospheric boundary layers: a trade wind cumulus layer, a stratocumulus layer, and a clear convective case. The new closures have shortcomings, but nevertheless are superior to the double or triple delta closures in most of the cases tested.
Association of current smoking with airway inflammation in chronic obstructive pulmonary disease and asymptomatic smokers
Authors: Willemse Brigitte WM , ten Hacken Nick HT , Rutgers Bea , Postma Dirkje S , Timens Wim 
Published: April 2005

Abstract
Background
Inflammation in the airways and lung parenchyma underlies fixed airway obstruction in chronic obstructive pulmonary disease. The exact role of smoking as promoting factor of inflammation in chronic obstructive pulmonary disease is not clear, partly because studies often do not distinguish between current and ex-smokers.

Methods
We investigated airway inflammation in sputum and bronchial biopsies of 34 smokers with chronic obstructive pulmonary disease (9 Global initiative for Chronic Obstructive Lung Disease stage 0, 9 stage I, 10 stage II and 6 stage III) and 26 asymptomatic smokers, and its relationship with past and present smoking habits and airway obstruction.

Results
Neutrophil percentage, interleukin-8 and eosinophilic-cationic-protein levels in sputum were higher in chronic obstructive pulmonary disease (stage I-III) than asymptomatic smokers. Inflammatory cell numbers in bronchial biopsies were similar in both groups. Current smoking correlated positively with macrophages: in bronchial biopsies in both groups, and in sputum in chronic obstructive pulmonary disease. Pack-years smoking correlated positively with biopsy macrophages only in chronic obstructive pulmonary disease.

Conclusion
Inflammatory effects of current smoking may mask the underlying ongoing inflammatory process pertinent to chronic obstructive pulmonary disease. This may have implications for future studies, which should avoid including mixed populations of smokers and ex-smokers.
Detailed protein sequence alignment based on Spectral Similarity Score (SSS)
Authors: Gupta Kshitiz , Thomas Dina , Vidya SV , Venkatesh KV , Ramakumar S 
Published: April 2005

Abstract
Background
The chemical property and biological function of a protein is a direct consequence of its primary structure. Several algorithms have been developed which determine alignment and similarity of primary protein sequences. However, character based similarity cannot provide insight into the structural aspects of a protein. We present a method based on spectral similarity to compare subsequences of amino acids that behave similarly but are not aligned well by considering amino acids as mere characters. This approach finds a similarity score between sequences based on any given attribute, like hydrophobicity of amino acids, on the basis of spectral information after partial conversion to the frequency domain.

Results
Distance matrices of various branches of the human kinome, that is the full complement of human kinases, were developed that matched the phylogenetic tree of the human kinome establishing the efficacy of the global alignment of the algorithm. PKCd and PKCe kinases share close biological properties and structural similarities but do not give high scores with character based alignments. Detailed comparison established close similarities between subsequences that do not have any significant character identity. We compared their known 3D structures to establish that the algorithm is able to pick subsequences that are not considered similar by character based matching algorithms but share structural similarities. Similarly many subsequences with low character identity were picked between xyna-theau and xyna-clotm F/10 xylanases. Comparison of 3D structures of the subsequences confirmed the claim of similarity in structure.

Conclusion
An algorithm is developed which is inspired by successful application of spectral similarity applied to music sequences. The method captures subsequences that do not align by traditional character based alignment tools but give rise to similar secondary and tertiary structures. The Spectral Similarity Score (SSS) is an extension to the conventional similarity methods and results indicate that it holds a strong potential for analysis of various biological sequences and structural variations in proteins.
Identification of a novel Rev-interacting cellular protein
Authors: Kramer-Hämmerle Susanne , Ceccherini-Silberstein Francesca , Bickel Christian , Wolff Horst , Vincendeau Michelle , Werner Thomas , Erfle Volker , Brack-Werner Ruth 
Published: April 2005

Abstract
Background
Human cell types respond differently to infection by human immunodeficiency virus (HIV). Defining specific interactions between host cells and viral proteins is essential in understanding how viruses exploit cellular functions and the innate strategies underlying cellular control of HIV replication. The HIV Rev protein is a post-transcriptional inducer of HIV gene expression and an important target for interaction with cellular proteins. Identification of Rev-modulating cellular factors may eventually contribute to the design of novel antiviral therapies.

Results
Yeast-two hybrid screening of a T-cell cDNA library with Rev as bait led to isolation of a novel human cDNA product (16.4.1). 16.4.1-containing fusion proteins showed predominant cytoplasmic localization, which was dependent on CRM1-mediated export from the nucleus. Nuclear export activity of 16.4.1 was mapped to a 60 amino acid region and a novel transport signal identified. Interaction of 16.4.1 with Rev in human cells was shown in a mammalian two-hybrid assay and by colocalization of Rev and 16.4.1 in nucleoli, indicating that Rev can recruit 16.4.1 to the nucleus/nucleoli. Rev-dependent reporter expression was inhibited by overexpressing 16.4.1 and stimulated by siRNAs targeted to 16.4.1 sequences, demonstrating that 16.4.1 expression influences the transactivation function of Rev.

Conclusion
These results suggest that 16.4.1 may act as a modulator of Rev activity. The experimental strategies outlined in this study are applicable to the identification and biological characterization of further novel Rev-interacting cellular factors.
Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition
Authors: Zeggini Eleftheria , Barton Anne , Eyre Stephen , Ward Daniel , Ollier William , Worthington Jane , John Sally 
Published: April 2005

Abstract
Background
The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map.

Results
Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent.

Conclusion
For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.
Investigating hookworm genomes by comparative analysis of two Ancylostoma species
Authors: Mitreva Makedonka , McCarter James P , Arasu Prema , Hawdon John , Martin John , Dante Mike , Wylie Todd , Xu Jian , Stajich Jason E , Kapulkin Wadim , Clifton Sandra W , Waterston Robert H , Wilson Richard K 
Published: April 2005

Abstract
Background
Hookworms, infecting over one billion people, are the mostly closely related major human parasites to the model nematode Caenorhabditis elegans. Applying genomics techniques to these species, we analyzed 3,840 and 3,149 genes from Ancylostoma caninum and A. ceylanicum.

Results
Transcripts originated from libraries representing infective L3 larva, stimulated L3, arrested L3, and adults. Most genes are represented in single stages including abundant transcripts like hsp-20 in infective L3 and vit-3 in adults. Over 80% of the genes have homologs in C. elegans, and nearly 30% of these were with observable RNA interference phenotypes. Homologies were identified to nematode-specific and clade V specific gene families. To study the evolution of hookworm genes, 574 A. caninum / A. ceylanicum orthologs were identified, all of which were found to be under purifying selection with distribution ratios of nonsynonymous to synonymous amino acid substitutions similar to that reported for C. elegans / C. briggsae orthologs. The phylogenetic distance between A. caninum and A. ceylanicum is almost identical to that for C. elegans / C. briggsae.

Conclusion
The genes discovered should substantially accelerate research toward better understanding of the parasites' basic biology as well as new therapies including vaccines and novel anthelmintics.
Relative transcript quantification by Quantitative PCR: Roughly right or precisely wrong?
Authors: Skern Rasmus , Frost Petter , Nilsen Frank 
Published: April 2005

Abstract
Background
When estimating relative transcript abundances by quantitative real-time PCR (Q-PCR) we found that the results can vary dramatically depending on the method chosen for data analysis.

Results
Analyses of Q-PCR results from a salmon louse starvation experiment show that, even with apparently good raw data, different analytical approaches [1, 2] may lead to opposing biological conclusions.

Conclusion
The results emphasise the importance of being cautious when analysing Q-PCR data and indicate that uncritical routine application of an analytical method will eventually result in incorrect conclusions. We do not know the extent of, or have a universal solution to this problem. However, we strongly recommend caution when analysing Q-PCR results e.g. by using two or more analytical approaches to validate conclusions. In our view a common effort should be made to standardise methods for analysis and validation of Q-PCR results.