bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the
metS
and
murB
Loci for Antibiotic Discovery Using Targeted Antisense RNA Expression Analysis in
Bacillus anthracis
Authors: Kedar G. C. , Brown-Driver Vickie , Reyes Daniel R. , Hilgers Mark T. , Stidham Mark A. , Shaw Karen Joy , Finn John , Haselbeck Robert J. 
Published: March 2007

ABSTRACT

The biowarfare-relevant bacterial pathogen
Bacillus anthracis
contains two paralogs each of the
metS
and
murB
genes, which encode the important antibiotic target functions methionyl-tRNA synthetase and UDP-
N
-acetylenolpyruvoylglucosamine reductase, respectively. Empirical screens were conducted to detect and characterize gene fragments of each of these four genes that could cause growth reduction of
B. anthracis
when inducibly expressed from a plasmid-borne promoter. Numerous such gene fragments that were overwhelmingly in the antisense orientation were identified for the
metS1
and
murB2
alleles, while no such orientation bias was seen for the
metS2
and
murB1
alleles. Gene replacement mutagenesis was used to confirm the essentiality of the
metS1
and
murB2
alleles, and the nonessentiality of the
metS2
and
murB1
alleles, for vegetative growth. Induced transcription of RNA from
metS1
and
murB2
antisense-oriented gene fragments resulted in specific reduction of mRNA of their cognate genes. Attenuation of MetS1 enzyme expression hypersensitized
B. anthracis
cells to a MetS-specific antimicrobial compound but not to other antibiotics that affect cell wall assembly, fatty acid biosynthesis, protein translation, or DNA replication. Antisense-dependent reduction of MurB2 enzyme expression caused hypersensitivity to beta-lactam antibiotics, a synergistic response that has also been noted for the MurA-specific antibiotic fosfomycin. These experiments form the basis of mode-of-action detection assays that can be used in the discovery of novel MetS- or MurB-specific antibiotic drugs that are effective against
B. anthracis
or other gram-positive bacterial pathogens.
Enteropathogenic
Escherichia coli
-Induced Epidermal Growth Factor Receptor Activation Contributes to Physiological Alterations in Intestinal Epithelial Cells
Authors: Roxas Jennifer L. , Koutsouris Athanasia , Viswanathan V. K. 
Published: March 2007

ABSTRACT

The diarrheagenic pathogen enteropathogenic
Escherichia coli
(EPEC) is responsible for significant infant mortality and morbidity, particularly in developing countries. EPEC pathogenesis relies on a type III secretion system-mediated transfer of virulence effectors into host cells. EPEC modulates host cell survival and inflammation, although the proximal signaling pathways have not been well defined. We therefore examined the effect of EPEC on the epidermal growth factor receptor (EGFR), a known upstream activator of both the prosurvival phosphoinositide 3-kinase/Akt and proinflammatory mitogen-activated protein (MAP) kinase pathways. EPEC induced the autophosphorylation of EGFR in intestinal epithelial cells within 15 min postinfection, with maximal phosphorylation being observed at 4 h. Filter-sterilized supernatants of EPEC cultures also stimulated EGFR phosphorylation, suggesting that a secreted component(s) contributes to this activity. EPEC-induced EGFR phosphorylation was blocked by the pharmacological inhibitor tyrphostin AG1478, as well as by EGFR-neutralizing antibodies. Inhibition of EGFR phosphorylation by AG1478 had no effect on bacterial adherence, actin recruitment to sites of attachment, or EPEC-induced epithelial barrier function alteration. EPEC-mediated Akt phosphorylation, however, was inhibited by both AG1478 and EGFR-neutralizing antibodies. Correspondingly, inhibition of EGFR activation increased the apoptosis/necrosis of infected epithelial cells. Inhibition of EGFR phosphorylation also curtailed EPEC-induced ERK1/2 (MAP kinase) phosphorylation and, correspondingly, the production of the proinflammatory cytokine interleukin-8 by infected epithelial cells. Our studies suggest that EGFR is a key proximal signaling molecule during EPEC pathogenesis.
Interaction ofCandida albicanswith Adherent Human Peripheral Blood Mononuclear Cells IncreasesC. albicansBiofilm Formation and Results in Differential Expression of Pro- and Anti-Inflammatory Cytokines
Authors: Chandra Jyotsna , McCormick Thomas S. , Imamura Yoshifumi , Mukherjee Pranab K. , Ghannoum Mahmoud A. 
Published: March 2007

ABSTRACTMonocytes and macrophages are the cell types most commonly associated with the innate immune response againstCandida albicansinfection. Interactions between the host immune system andCandidaorganisms have been investigated for planktonicCandidacells, but no studies have addressed these interactions in a biofilm environment. In this study, for the first time, we evaluated the ability ofC. albicansto form biofilms in the presence or absence of adherent peripheral blood mononuclear cells (PBMCs; enriched for monocytes and macrophages by adherence). Our analyses using scanning electron and confocal scanning laser microscopy showed that the presence of PBMCs enhanced the ability ofC. albicansto form biofilms and that the majority of PBMCs were localized to the basal and middle layers of the biofilm. In contrast to the interactions of PBMCs with planktonicC. albicans, where PBMCs phagocytose fungal cells, PBMCs did not appear to phagocytose fungal cells in biofilms. Furthermore, time-lapse laser microscopy revealed dynamic interactions betweenC. albicansand PBMCs in a biofilm. Additionally, we found that (i) only viable PBMCs influenceCandidabiofilm formation, (ii) cell surface components of PBMCs did not contribute to the enhancement ofC. albicansbiofilm, (iii) the biofilm-enhancing effect of PBMCs is mediated by a soluble factor released into the coculture medium of PBMCs withC. albicans, and (iv) supernatant collected from this coculture contained differential levels of pro- and anti-inflammatory cytokines. Our studies provide new insight into the interaction betweenCandidabiofilm and host immune cells and demonstrate that immunocytes may influence the ability ofC. albicansto form biofilms.
Live Attenuated
Streptococcus pneumoniae
Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice
Authors: Roche Aoife M. , King Samantha J. , Weiser Jeffrey N. 
Published: March 2007

ABSTRACT

Streptococcus pneumoniae
is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of
S. pneumoniae
containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (
cps
), pneumolysin (
ply
), and pneumococcal surface protein A (
pspA
). Both the
cps
and
ply/pspA
mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with
cps
mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as μMT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated
S. pneumoniae
is a potentially safe and less complex vaccine strategy that may offer broad protection.
Revisiting the Possible Links between the Quasi-Biennial Oscillation and the Indian Summer Monsoon Using NCEP R-2 and CMAP Fields
Authors: Claud Chantal , Terray Pascal 
Published: March 2007

AbstractIn the past the stratospheric quasi-biennial oscillation (QBO) has sometimes been proposed to explain the tendency for the Indian summer monsoon (ISM) to alternate between strong and weak years. In this study, NCEP Reanalysis-2 (R-2) and Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) fields are statistically analyzed to assess the relationship between equatorial zonal winds in the stratosphere and ISM. In a first step, it is shown that zonal winds at 15 hPa during the preceding winter (January–February) are the best stratospheric predictor of the summer rainfall over the Indian subcontinent as a whole. This relationship mainly holds for August and September, or the late ISM. Surprisingly, the QBO pattern is not significantly associated with the rainfall variability during June–July or the early ISM. CMAP and NCEP R-2 fields corroborate these findings and show that westerly QBO years are associated with a deepening of the monsoon trough over the Gangetic plains and decreased convective activity in the eastern equatorial Indian region. However, further statistical analysis shows that the QBO–ISM link is complex since a westerly QBO phase at 15 hPa in boreal winter leads to a weaker monsoon surface circulation with, in particular, a weakening of the Somali jet at the beginning of the monsoon, but a much stronger circulation in September. At that time, the Tibetan high is reinforced, the tropical easterly jet at 200 hPa is stronger over India, and the local reversed Hadley circulation is also strengthened north of the equator. The mechanisms by which the QBO may affect ISM have been explored through, in particular, correlations between stratospheric winds and tropopause temperature and pressure fields. The results provide support for an out-of-phase behavior of convective activity between the Indian subcontinent and the equatorial Indian Ocean induced by the QBO phase, especially during the late ISM. During a westerly QBO phase, convective activity is, in September, enhanced over India, which brings higher precipitation, compared to the east phase. This work also suggests that the winter QBO at 15 hPa could have some skill in foreshadowing the late ISM.
Idealized Hot Spot Experiments with a General Circulation Model
Authors: Maloney Eric D. , Sobel Adam H. 
Published: March 2007

Abstract
Idealized experiments are conducted using a GCM coupled to a 20-m slab ocean model to examine the short-term response to an initial localized positive equatorial SST anomaly, or “hot spot.” A hot spot is imposed upon an aquaplanet with globally uniform 28°C SST, insolation, and trace gas concentrations designed to mimic tropical warm pool conditions. No boundary condition or external parameter other than the Coriolis parameter varies with latitude. A 15-member ensemble is initiated using random atmospheric initial conditions. A 2°C equatorial warm anomaly is switched on, along with ocean coupling (day 0).
Enhanced deep convection rapidly develops near the hot spot, forcing an anomalous large-scale circulation that resembles the linear response of a dry atmosphere to a localized heating, as in the Gill model. Enhanced convection, the anomalous large-scale circulation, and enhanced wind speed peak in amplitude at about day 15. Enhanced latent heat fluxes driven primarily by an increase in vector mean wind damp the anomalous heat content of the ocean near the hot spot before day 20. Between day 20 and day 50, suppressed latent heat fluxes due to suppressed synoptic eddy variance cause a warming of the remote Tropics in regions of anomalous low-level easterly flow. This wind-driven evaporative atmosphere–ocean exchange results in a 60–70-day oscillation in tropical mean oceanic heat content, accompanied by a compensating out-of-phase oscillation in vertically integrated atmospheric moist static energy. Beyond day 70 of the simulation, positive SST anomalies are found across much of the tropical belt. These slowly decay toward the 28°C background state.
Comparison of protein structures by growing neighborhood alignments
Authors: Bhattacharya Sourangshu , Bhattacharyya Chiranjib , Chandra Nagasuma R 
Published: March 2007

Abstract

Background
Design of protein structure comparison algorithm is an important research issue, having far reaching implications. In this article, we describe a protein structure comparison scheme, which is capable of detecting correct alignments even in difficult cases, e.g. non-topological similarities. The proposed method computes protein structure alignments by comparing, small substructures, called neighborhoods. Two different types of neighborhoods, sequence and structure, are defined, and two algorithms arising out of the scheme are detailed. A new method for computing equivalences having non-topological similarities from pairwise similarity score is described. A novel and fast technique for comparing sequence neighborhoods is also developed.

Results
The experimental results show that the current programs show better performance on Fischer and Novotny's benchmark datasets, than state of the art programs, e.g. DALI, CE and SSM. Our programs were also found to calculate correct alignments for proteins with huge amount of indels and internal repeats. Finally, the sequence neighborhood based program was used in extensive fold and non-topological similarity detection experiments. The accuracy of the fold detection experiments with the new measure of similarity was found to be similar or better than that of the standard algorithm CE.

Conclusion
A new scheme, resulting in two algorithms, have been developed, implemented and tested. The programs developed are accessible at http://mllab.csa.iisc.ernet.in/mp2/runprog.html.
Are patients with non-ST elevation myocardial infarction undertreated?
Authors: Rasoul Saman , Ottervanger Jan Paul , Dambrink Jan-Henk E , de Boer Menko-Jan , Hoorntje Jan CA , Gosselink AT Marcel , Zijlstra Felix , Suryapranata Harry , van't Hof Arnoud WJ 
Published: March 2007

Abstract

Background
The worse prognosis in patients without ST-elevation (non-STEMI) as compared to ST-elevation myocardial infarction (STEMI), may be due to treatment differences. We aimed to evaluate the differences in characteristics, treatment and outcome in patients with non-STEMI versus STEMI in an unselected patient population.

Methods
Individual patient data from all patients in our hospital with a discharge diagnosis of MI between Jan 2001 and Jan 2002 were evaluated. Follow-up data were obtained until December 2004. Patients were categorized according to the presenting electrocardiogram into non-STEMI or STEMI.

Results
A total of 824 patients were discharged with a diagnosis of MI, 29% with non-STEMI and 71% with STEMI. Patients with non-STEMI were significantly older and had a higher cardiovascular risk profile. They underwent less frequently coronary angiography and revascularization and received less often clopidogrel and ACE-inhibitor on discharge. Long-term mortality was significantly higher in the non-STEMI patients as compared to STEMI patients, 20% vs. 12%, p = 0.006, respectively. However, multivariate analysis showed that age, diabetes, hypertension and no reperfusion therapy (but not non-STEMI presentation) were independent and significant predictors of long-term mortality.

Conclusion
In an unselected cohort of patients discharged with MI, there were significant differences in baseline characteristics, and (invasive) treatment between STEMI and non-STEMI. Long-term mortality was also different, but this was due to differences in baseline characteristics and treatment. More aggressive treatment may improve outcome in non-STEMI patients.
Generalist care managers for the treatment of depressed medicaid patients in North Carolina: A pilot study
Authors: Landis Suzanne E , Gaynes Bradley N , Morrissey Joseph P , Vinson Nina , Ellis Alan R , Domino Marisa E 
Published: March 2007

Abstract

Background
In most states, mental illness costs are an increasing share of Medicaid expenditures. Specialized depression care managers (CM) have consistently demonstrated improvements in patient outcomes relative to usual primary care (UC), but are costly and may not be fully utilized in smaller practices. A generalist care manager (GCM) could manage multiple chronic conditions and be more accepted and cost-effective than the specialist depression CM. We designed a pilot program to demonstrate the feasibility of training/deploying GCMs into primary care settings.

Methods
We randomized depressed adult Medicaid patients in 2 primary care practices in Western North Carolina to a GCM intervention or to UC. GCMs, already providing services in diabetes and asthma in both study arms, were further trained to provide depression services including self-management, decision support, use of information systems, and care management. The following data were analyzed: baseline, 3- and 6-month Patient Health Questionnaire (PHQ9) scores; baseline and 6-month Short Form (SF) 12 scores; Medicaid claims data; questionnaire on patients' perceptions of treatment; GCM case notes; physician and office staff time study; and physician and office staff focus group discussions.

Results
Forty-five patients were enrolled, the majority with preexisting depression. Both groups improved; the GCM group did not demonstrate better clinical and functional outcomes than the UC group. Patients in the GCM group were more likely to have prescriptions of correct dosing by chart data. GCMs most often addressed comorbid conditions (36%), then social issues (27%) and appointment reminders (14%). GCMs recorded an average of 46 interactions per patient in the GCM arm. Focus group data demonstrated that physicians valued using GCMs. A time study documented that staff required no more time interacting with GCMs, whereas physicians spent an average of 4 minutes more per week.

Conclusion
GCMs can be trained in care of depression and other chronic illnesses, are acceptable to practices and patients, and result in physicians prescribing guideline concordant care. GCMs appear to be a feasible intervention for community medical practices and to warrant a larger scale trial to test their appropriateness for Medicaid programs nationally.
Classical Genetic and Quantitative Trait Loci Analyses of Heterosis in a Maize Hybrid Between Two Elite Inbred Lines
Authors: Frascaroli Elisabetta , Canè Maria Angela , Landi Pierangelo , Pea Giorgio , Gianfranceschi Luca , Villa Marzio , Morgante Michele , Pè Mario Enrico 
Published: March 2007

Abstract
The exploitation of heterosis is one of the most outstanding advancements in plant breeding, although its genetic basis is not well understood yet. This research was conducted on the materials arising from the maize single cross B73 × H99 to study heterosis by procedures of classical genetic and quantitative trait loci (QTL) analyses. Materials were the basic generations, the derived 142 recombinant inbred lines (RILs), and the three testcross populations obtained by crossing the 142 RILs to each parent and their F1. For seedling weight (SW), number of kernels per plant (NK), and grain yield (GY), heterosis was &gt;100% and the average degree of dominance was &gt;1. Epistasis was significant for SW and NK but not for GY. Several QTL were identified and in most cases they were in the additive–dominance range for traits with low heterosis and mostly in the dominance–overdominance range for plant height (PH), SW, NK, and GY. Only a few QTL with digenic epistasis were identified. The importance of dominance effects was confirmed by highly significant correlations between heterozygosity level and phenotypic performance, especially for GY. Some chromosome regions presented overlaps of overdominant QTL for SW, PH, NK, and GY, suggesting pleiotropic effects on overall plant vigor.
Experimental Estimate of the Abundance and Effects of Nearly Neutral Mutations in the RNA Virus ϕ6
Authors: Burch Christina L , Guyader Sebastien , Samarov Daniel , Shen Haipeng 
Published: March 2007

AbstractAlthough the frequency and effects of neutral and nearly neutral mutations are critical to evolutionary patterns and processes governed by genetic drift, the small effects of such mutations make them difficult to study empirically. Here we present the results of a mutation-accumulation experiment designed to assess the frequencies of deleterious mutations with undetectable effects. We promoted the accumulation of spontaneous mutations by subjecting independent lineages of the RNA virus ϕ6 to repeated population bottlenecks of a single individual. We measured fitness following every bottleneck to obtain a complete picture of the timing and effects of the accumulated mutations with detectable effects and sequenced complete genomes to determine the number of mutations that were undetected by the fitness assays. To estimate the effects of the undetected mutations, we implemented a likelihood model developed for quantitative trait locus (QTL) data (Otto and Jones 2000) to estimate the number and effects of the undetected mutations from the measured number and effects of the detected mutations. Using this method we estimated a deleterious mutation rate of U = 0.03 and a gamma effects distribution with mean $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\bar{s}}{=}0.093\) \end{document}$ and coefficient of variation = 0.204. Although our estimates of U and $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\bar{s}}\) \end{document}$ fall within the range of recent mutation rate and effect estimates in eukaryotes, the fraction of mutations with detectable effects on laboratory fitness (39%) appears to be far higher in ϕ6 than in eukaryotes.
The Caenorhabditis elegans Rad17 Homolog HPR-17 Is Required for Telomere Replication
Authors: Boerckel Julie , Walker Dana , Ahmed Shawn 
Published: March 2007

Abstract
Subunits of the Rad9/Rad1/Hus1 (9-1-1) proliferating cell nuclear antigen (PNCA)-like sliding clamp are required for DNA damage responses and telomerase-mediated telomere replication in the nematode Caenorhabditis elegans. PCNA sliding clamps are loaded onto DNA by a replication factor C (RFC) clamp loader. The C. elegans Rad17 RFC clamp loader homolog, hpr-17, functions in the same pathway as the 9-1-1 complex with regard to both the DNA damage response and telomerase-mediated telomere elongation. Thus, hpr-17 defines an RFC-like complex that facilitates telomerase activity in vivo in C. elegans.
N,N,N′,N′,N″‐Pentamethyl‐N″‐[(trifluorosilyl)methyl] phosphoric triamide. First example of the existence of intramolecular PO→Si coordination bond in the Si‐containing phosphoric triamides
Authors: Lazareva Nataliya F. , Albanov Alexander I. , Lazarev Igor M. , Pestunovich Vadim A. 
Published: March 2007

AbstractThe N,N,N′,N′,N″‐pentamethyl‐N″‐(trifluorosilylmethyl)phosphoric triamide OP(NMe2)2N(Me) CH2SiF3 with intramolecular PO→Si coordination was formed by the reaction of N,N,N′,N′,N″‐pentamethyl‐N″[(triethoxysilyl)methyl]phosphoric triamide with BF3·Et2O. Copyright © 2007 John Wiley & Sons, Ltd.