bluuebunny/crossref_metadata_2025_split huggingface dataset:
NURSE STRESS IN HOSPITAL AND SATELLITE HAEMODIALYSIS UNITS
Authors: Dermody Kirsten , Bennett Paul N. 
Published: March 2008

SUMMARYAim: To explore nurse stress in both in‐centre hospital haemodialysis and satellite haemodialysis unit in an Australian city's health service.Method: Focus groups from both in‐centre and satellite dialysis units were undertaken followed by questionnaires generated by the focus group data.Results: In‐centre nursing staff rated the busyness of the unit as the maximum stress and stated that they felt this high level of stress on a daily basis. The most notable stressor for the staff at the satellite unit related to patient behaviour and the perceived unrealistic expectations of the patient followed by patients arriving unwell at the unit.Conclusion: Nurses suffer stress on a daily basis in both in‐centre and satellite dialysis units. The major stressors differ from in‐centre to satellite dialysis units.
Synergistic premalignant effects of chronic ethanol exposure and insulin receptor substrate‐1 overexpression in liver
Authors: Longato Lisa , De La Monte Suzanne , Califano Sophia , Wands Jack R. 
Published: March 2008

Aim:  Insulin receptor substrate, type 1 (IRS‐1) transmits growth and survival signals, and is overexpressed in more than 90% of hepatocellular carcinomas (HCCs). However, experimental overexpression of IRS‐1 in the liver was found not to be sufficient to cause HCC. Since chronic alcohol abuse is a risk factor for HCC, we evaluated potential interactions between IRS‐1 overexpression and chronic ethanol exposure by assessing premalignant alterations in gene expression.Methods:  Wild‐type (wt) or IRS‐1 transgenic (Tg) mice, constitutively overexpressing the human (h) transgene in the liver, were pair‐fed isocaloric liquid diets containing 0% or 24% ethanol for 8 weeks. The livers were used for histopathologic study and gene expression analysis, focusing on insulin, insulin‐like growth factor (IGF) and wingless (WNT)–Frizzled (FZD) pathways, given their known roles in HCC.Results:  In wt mice, chronic ethanol exposure caused hepatocellular microsteatosis with focal chronic inflammation, reduced expression of proliferating cell nuclear antigen (PCNA) and increased expression of IGF‐I and IGF‐I receptor. In hIRS‐1 Tg mice, chronic ethanol exposure caused hepatic micro‐ and macrosteatosis, focal chronic inflammation, apoptosis and disordered lobular architecture. These effects of ethanol in hIRS‐1 Tg mice were associated with significantly increased expression of IGF‐II, insulin, IRS‐4, aspartyl–asparaginyl β hydroxylase (AAH), WNT‐1 and FZD 7, as occurs in HCC.Conclusion:  In otherwise normal liver, chronic ethanol exposure mainly causes liver injury and inflammation with impaired DNA synthesis. In contrast, in the context of hIRS‐1 overexpression, chronic ethanol exposure may serve as a cofactor in the pathogenesis of HCC by promoting expression of growth factors, receptors and signaling molecules known to be associated with hepatocellular transformation.
Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to
Streptococcus pyogenes
in Children
Authors: Pichichero M. E. , Casey J. R. , Block S. L. , Guttendorf R. , Flanner H. , Markowitz D. , Clausen S. 
Published: March 2008

ABSTRACT

An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (
T
>MIC; based on the MIC
90
of 0.06 μg/ml for
Streptococcus pyogenes
reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily
T
>MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, −12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of ≥85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to
S. pyogenes
. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, −11.6% to −0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily
T
>MIC
90
more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total
T
>MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.
Buthionine Sulfoximine Has Anti-
Trypanosoma cruzi
Activity in a Murine Model of Acute Chagas' Disease and Enhances the Efficacy of Nifurtimox
Authors: Faúndez Mario , López-Muñoz Rodrigo , Torres Gloria , Morello Antonio , Ferreira Jorge , Kemmerling Ulrike , Orellana Myriam , Maya Juan D. 
Published: March 2008

ABSTRACT

l
-Buthionine (
S
,
R
)-sulfoximine (BSO) at a dose of 220 mg/kg of body weight/day showed an anti-
Trypanosoma cruzi
effect in infected mice, increasing their survival rate and decreasing the parasitemias and parasite burden in the hearts. Treatment with BSO plus nifurtimox caused an increase in the survival rate in comparison to the rates with treatment with each drug alone.
Toll-Like Receptor 9-Dependent Immune Activation by Unmethylated CpG Motifs in
Aspergillus fumigatus
DNA
Authors: Ramirez-Ortiz Zaida G. , Specht Charles A. , Wang Jennifer P. , Lee Chrono K. , Bartholomeu Daniella C. , Gazzinelli Ricardo T. , Levitz Stuart M. 
Published: March 2008

ABSTRACT

Phagocytic defenses are critical for effective host defenses against the opportunistic fungal pathogen
Aspergillus fumigatus
. Previous studies found that following challenge with
A. fumigatus
, Toll-like receptor 9 (TLR9) knockout mice survived longer than wild-type mice. However, the mechanism responsible was not defined. Here we demonstrate that
A. fumigatus
contains unmethylated CpG sequences, the natural ligands for TLR9.
A. fumigatus
DNA and synthetic CpG-rich oligodeoxynucleotides (ODNs) containing sequences found in the
A. fumigatus
genome potently stimulated the production of proinflammatory cytokines in mouse bone marrow-derived dendritic cells (BMDCs) and human plasmacytoid dendritic cells. The response was decreased when the fungal DNA was treated with a CpG methylase or with CpG-specific endonucleases. A role for TLR9 was demonstrated as cytokine production was abolished in BMDCs from TLR9-deficient mice. Moreover, transfection of HEK293 cells with human TLR9 conferred responsiveness to synthetic CpG-rich ODNs containing sequences found in
A. fumigatus
DNA. Taken together, these data demonstrate that TLR9 detects
A. fumigatus
DNA, resulting in the secretion of proinflammatory cytokines, which may contribute to the immune response to the pathogen.
Single Nucleotide Polymorphisms That Cause Structural Changes in the Cyclic AMP Receptor Protein Transcriptional Regulator of the Tuberculosis Vaccine Strain
Mycobacterium bovis
BCG Alter Global Gene Expression without Attenuating Growth
Authors: Hunt Debbie M. , Saldanha José W. , Brennan John F. , Benjamin Pearline , Strom Molly , Cole Jeffrey A. , Spreadbury Claire L. , Buxton Roger S. 
Published: March 2008

ABSTRACT

Single nucleotide polymorphisms (SNPs) are present in the global transcriptional regulator cyclic AMP (cAMP) receptor protein (CRP) of the attenuated vaccine strain
Mycobacterium bovis
, bacillus Calmette-Guérin (BCG). We have found that these SNPs resulted in small but significant changes in the expression of a number of genes in
M. tuberculosis
when a deletion of the Rv3676 CRP was complemented by the BCG allele, compared to complementation by the
M. tuberculosis
allele. We can explain these changes in gene expression by modeling the structure of the mycobacterial protein on the known structure of CRP from
Escherichia coli
. Thus, the SNP change in the DNA-binding domain, Lys178, is predicted to form a hydrogen bond with the phosphate backbone of the DNA, as does the equivalent residue in
E. coli
, whereas Glu178 in
M. tuberculosis
/
M. bovis
does not, thus explaining the stronger binding reported for CRP of BCG to CRP-binding sites in mycobacterial DNA. In contrast, the SNP change in the nucleotide binding domain (Leu47Pro) is predicted to result in the loss of one hydrogen bond, which is accommodated by the structure, and would not therefore be expected to cause any change in function relating to cAMP binding. The BCG allele fully complemented the growth defect caused by the deletion of the Rv3676 protein in
M. tuberculosis
, both in vitro and in macrophage and mouse infections, suggesting that these SNPs do not play any role in the attenuation of BCG. However, they may have allowed BCG to grow better under the in vitro-selective conditions used in its derivation from the
M. bovis
wild type.
The Intrinsic Immunoglobulin G Endopeptidase Activity of Streptococcal Mac-2 Proteins Implies a Unique Role for the Enzymatically Impaired Mac-2 Protein of M28 Serotype Strains
Authors: Söderberg Jenny Johansson , Engström Patrik , von Pawel-Rammingen Ulrich 
Published: March 2008

ABSTRACT

IdeS, a secreted cysteine protease of the important human pathogen
Streptococcus pyogenes
, interferes with phagocytic killing by specifically cleaving the heavy chain of immunoglobulin G (IgG). Two allelic variants of the enzyme have been described, the IgG-specific endopeptidase, IdeS (or Mac-1) and Mac-2, a protein with only weak IgG endopeptidase activity, which has been suggested to interfere with opsonophagocytosis by blocking Fcγ receptors of phagocytic cells. However, despite the fact that Mac-2 proteins interact with Fcγ receptors, no inhibition of reactive oxygen species (ROS) production, opsonophagocytosis, or streptococcal killing by Mac-2 has been reported. In the present study, Mac-2 proteins are shown to contain IgG endopeptidase activity indistinguishable from the enzymatic activity exhibited by IdeS/Mac-1 proteins. The earlier reported weak IgG endopeptidase activity appears to be unique to Mac-2 of M28 serotype strains (Mac-2
M28
) and is most likely due to the formation of a disulfide bond between the catalytic site cysteine and a cysteine residue in position 257 of Mac-2
M28
. Furthermore, Mac-2 proteins are shown to inhibit ROS production ex vivo, independently of the IgG endopeptidase activity of the proteins. Inhibition of ROS generation per se, however, was not sufficient to mediate streptococcal survival in bactericidal assays. Thus, in contrast to earlier studies, implicating separate functions for IdeS and Mac-2 protein variants, the current study suggests that Mac-2 and IdeS are bifunctional proteins, combining Fcγ receptor binding and IgG endopeptidase activity. This finding implies a unique role for Mac-2 proteins of the M28 serotype, since this serotype has evolved and retained a Mac-2 protein lacking IgG endopeptidase activity.
On the Differences in Storm Rainfall from Hurricanes Isidore and Lili. Part I: Satellite Observations and Rain Potential
Authors: Jiang Haiyan , Halverson Jeffrey B. , Simpson Joanne 
Published: March 2008

Abstract
It has been well known for years that the heavy rain and flooding of tropical cyclones over land bear a weak relationship to the maximum wind intensity. The rainfall accumulation history and rainfall potential history of two North Atlantic hurricanes during 2002 (Isidore and Lili) are examined using a multisatellite algorithm developed for use with the Tropical Rainfall Measuring Mission (TRMM) dataset. This algorithm uses many channel microwave data sources together with high-resolution infrared data from geosynchronous satellites and is called the real-time Multisatellite Precipitation Analysis (MPA-RT). MPA-RT rainfall estimates during the landfalls of these two storms are compared with the combined U.S. Next-Generation Doppler Radar (NEXRAD) and gauge dataset: the National Centers for Environmental Prediction (NCEP) hourly stage IV multisensor precipitation estimate analysis. Isidore produced a much larger storm total volumetric rainfall as a greatly weakened tropical storm than did category 1 Hurricane Lili during landfall over the same area. However, Isidore had a history of producing a large amount of volumetric rain over the open gulf. Average rainfall potential during the 4 days before landfall for Isidore was over a factor of 2.5 higher than that for Lili. When using the TRMM-based MPA-RT rainfall estimate, results are consistent with a previous study, which analyzed just the infrared-based rain estimation; that is, the rain potential history could be used as a predictor for the storm’s potential for inland flooding 3–4 days in advance of landfall.
A Comparison of Two Tropical Cyclone Bogussing Schemes
Authors: Wang Dongliang , Liang Xudong , Zhao Ying , Wang Bin 
Published: March 2008

Abstract
The impact of two bogussing schemes on tropical cyclone (TC) forecasts is compared. One scheme for bogussing TCs into the initial conditions of the nonhydrostatic version of the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) is proposed by NCAR and the Air Force Weather Agency (AFWA), and four-dimensional variational data assimilation technology is employed for the other bogus data assimilation (BDA) scheme. The initial vortex structure adjusted by the NCAR–AFWA (N–A) scheme is more physically realistic, while the BDA scheme produces an initial vortex structure that is more consistent with the model. The results from 41 forecasts of TCs occurring over the western North Pacific (WNP) in 2002 suggest that the adjustment of the initial structure in the BDA scheme produces a greater benefit to the subsequent track and intensity forecasts, and the improvements in the track and intensity forecasts are significant using the BDA scheme. It seems that when using a model with 45-km grid length, the N–A scheme has a negative impact on the track forecasts for the recurving TCs and on the intensity predictions after 24 h.
Spring and Summer Severe Weather Reports over the Midwest as a Function of Convective Mode: A Preliminary Study
Authors: Gallus William A. , Snook Nathan A. , Johnson Elise V. 
Published: March 2008

Abstract
Radar data during the period 1 April–31 August 2002 were used to classify all convective storms occurring in a 10-state region of the central United States into nine predominant morphologies, and the severe weather reports associated with each morphology were then analyzed. The morphologies included three types of cellular convection (individual cells, clusters of cells, and broken squall lines), five types of linear systems (bow echoes, squall lines with trailing stratiform rain, lines with leading stratiform rain, lines with parallel stratiform rain, and lines with no stratiform rain), and nonlinear systems. Because linear systems with leading and line-parallel stratiform rainfall were relatively rare in the 2002 sample of 925 events, 24 additional cases of these morphologies from 1996 and 1997 identified by Parker and Johnson were included in the sample.
All morphologies were found to pose some risk of severe weather, but substantial differences existed between the number and types of severe weather reports and the different morphologies. Normalizing results per event, nonlinear systems produced the fewest reports of hail, and were relatively inactive for all types of severe weather compared to the other morphologies. Linear systems generated large numbers of reports from all categories of severe weather. Among linear systems, the hail and tornado threat was particularly enhanced in systems having leading and line-parallel stratiform rain. Bow echoes were found to produce far more severe wind reports than any other morphology. The flooding threat was largest in broken lines and linear systems having trailing and line-parallel stratiform rain. Cellular storms, despite much smaller areal coverage, also were abundant producers of severe hail and tornadoes, particularly in broken squall lines.
PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages
Authors: Ng Felicia , Boucher Shayne , Koh Susie , Sastry Konduru S. R. , Chase Lucas , Lakshmipathy Uma , Choong Cleo , Yang Zheng , Vemuri Mohan C. , Rao Mahendra S. , Tanavde Vivek 
Published: March 2008

Abstract
We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)–β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.
PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system
Authors: Droit Arnaud , Hunter Joanna M , Rouleau Michèle , Ethier Chantal , Picard-Cloutier Aude , Bourgais David , Poirier Guy G 
Published: March 2008

Abstract

Background
In the "post-genome" era, mass spectrometry (MS) has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools.

Description
We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified.

Conclusion
Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.
Moraxella osloensis Gene Expression in the Slug Host Deroceras reticulatum
Authors: An Ruisheng , Sreevatsan Srinand , Grewal Parwinder S 
Published: March 2008

Abstract

Background
The bacterium Moraxella osloensis is a mutualistic symbiont of the slug-parasitic nematode Phasmarhabditis hermaphrodita. In nature, P. hermaphrodita vectors M. osloensis into the shell cavity of the slug host Deroceras reticulatum in which the bacteria multiply and kill the slug. As M. osloensis is the main killing agent, genes expressed by M. osloensis in the slug are likely to play important roles in virulence. Studies on pathogenic interactions between bacteria and lower order hosts are few, but such studies have the potential to shed light on the evolution of bacterial virulence. Therefore, we investigated such an interaction by determining gene expression of M. osloensis in its slug host D. reticulatum by selectively capturing transcribed sequences.

Results
Thirteen M. osloensis genes were identified to be up-regulated post infection in D. reticulatum. Compared to the in vitro expressed genes in the stationary phase, we found that genes of ubiquinone synthetase (ubiS) and acyl-coA synthetase (acs) were up-regulated in both D. reticulatum and stationary phase in vitro cultures, but the remaining 11 genes were exclusively expressed in D. reticulatum and are hence infection specific. Mutational analysis on genes of protein-disulfide isomerase (dsbC) and ubiS showed that the virulence of both mutants to slugs was markedly reduced and could be complemented. Further, compared to the growth rate of wild-type M. osloensis, the dsbC and ubiS mutants showed normal and reduced growth rate in vitro, respectively.

Conclusion
We conclude that 11 out of the 13 up-regulated M. osloensis genes are infection specific. Distribution of these identified genes in various bacterial pathogens indicates that the virulence genes are conserved among different pathogen-host interactions. Mutagenesis, growth rate and virulence bioassays further confirmed that ubiS and dsbC genes play important roles in M. osloensis survival and virulence, respectively in D. reticulatum.