bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic AMP Receptor Protein Regulates
cspE
, an Early Cold-Inducible Gene, in Escherichia coli
Authors: Uppal Sheetal , Maurya Svetlana R. , Hire Ramesh S. , Jawali Narendra 
Published: September 2011

ABSTRACT

cspE
, a member of the
cspA
family of cold shock proteins in
Escherichia coli
, is an early cold-inducible protein. The nucleic acid melting ability and transcription antiterminator activity of CspE have been reported to be critical for growth at low temperature. Here, we show that the cyclic AMP receptor protein (CRP), a global regulator involved in sugar metabolism, upregulates
cspE
in
E. coli
. Sequence analysis of the
cspE
upstream region revealed a putative CRP target site centered at −61.5 relative to the transcription start. The binding of CRP to this target site was demonstrated using electrophoretic mobility shift assays. The presence of this site was shown to be essential for P

cspE

activation by CRP. Mutational analysis of the binding site indicated that the presence of an intact second core motif is more important than the first core motif for CRP-P

cspE

interaction. Based on the promoter architecture, we classified P

cspE

as a class I CRP-dependent promoter. This was further substantiated by our data demonstrating the involvement of the AR1 domain of CRP in P

cspE

transcription. Furthermore, the substitutions in the key residues of the RNA polymerase α-subunit C-terminal domain (α-CTD), which are important for class I CRP-dependent transcription, showed the involvement of 265 and 287 determinants in P

cspE

transcription. In addition, the deletion of
crp
led to a growth defect at low temperature, suggesting that CRP plays an important role in cold adaptation.
The CgrA and CgrC Proteins Form a Complex That Positively Regulates
cupA
Fimbrial Gene Expression in Pseudomonas aeruginosa
Authors: McManus Heather R. , Dove Simon L. 
Published: September 2011

ABSTRACT

The CgrA and CgrC proteins of
Pseudomonas aeruginosa
are coregulators that are required for the phase-variable expression of the
cupA
fimbrial genes. Neither CgrA nor CgrC resembles a classical transcription regulator, and precisely how these proteins exert their regulatory effects on
cupA
gene expression is poorly understood. Here, we show that CgrA and CgrC interact with one another directly. We identify a mutant of CgrC that is specifically defective for interaction with CgrA and demonstrate that this mutant cannot restore the phase-variable expression of the
cupA
fimbrial genes to cells of a
cgrC
mutant strain. Using this mutant, we also show that CgrC associates with the
cupA
promoter regardless of whether or not it interacts with CgrA. Our findings establish that interaction between CgrA and CgrC is required for the phase-variable expression of the
cupA
fimbrial genes and suggest that CgrC exerts its regulatory effects directly at the
cupA
promoter, possibly by recruiting CgrA. Because the regions of CgrA and CgrC that we have identified as interacting with one another are highly conserved among orthologs, our findings raise the possibility that CgrA- and CgrC-related regulators present in other bacteria function coordinately through a direct protein-protein interaction.
RpiR Homologues May Link Staphylococcus aureus RNAIII Synthesis and Pentose Phosphate Pathway Regulation
Authors: Zhu Yefei , Nandakumar Renu , Sadykov Marat R. , Madayiputhiya Nandakumar , Luong Thanh T. , Gaupp Rosmarie , Lee Chia Y. , Somerville Greg A. 
Published: September 2011

ABSTRACT

Staphylococcus aureus
is a medically important pathogen that synthesizes a wide range of virulence determinants. The synthesis of many staphylococcal virulence determinants is regulated in part by stress-induced changes in the activity of the tricarboxylic acid (TCA) cycle. One metabolic change associated with TCA cycle stress is an increased concentration of ribose, leading us to hypothesize that a pentose phosphate pathway (PPP)-responsive regulator mediates some of the TCA cycle-dependent regulatory effects. Using bioinformatics, we identified three potential ribose-responsive regulators that belong to the RpiR family of transcriptional regulators. To determine whether these RpiR homologues affect PPP activity and virulence determinant synthesis, the
rpiR
homologues were inactivated, and the effects on PPP activity and virulence factor synthesis were assessed. Two of the three homologues (RpiRB and RpiRC) positively influence the transcription of the PPP genes
rpiA
and
zwf
, while the third homologue (RpiRA) is slightly antagonistic to the other homologues. In addition, inactivation of RpiRC altered the temporal transcription of RNAIII, the effector molecule of the
agr
quorum-sensing system. These data confirm the close linkage of central metabolism and virulence determinant synthesis, and they establish a metabolic override for quorum-sensing-dependent regulation of RNAIII transcription.
Bacillus subtilis σ
V
Confers Lysozyme Resistance by Activation of Two Cell Wall Modification Pathways, Peptidoglycan O-Acetylation and
d
-Alanylation of Teichoic Acids
Authors: Guariglia-Oropeza Veronica , Helmann John D. 
Published: September 2011

ABSTRACT

The seven extracytoplasmic function (ECF) sigma (σ) factors of
Bacillus subtilis
are broadly implicated in resistance to antibiotics and other cell envelope stressors mediated, in part, by regulation of cell envelope synthesis and modification enzymes. We here define the regulon of σ
V
as including at least 20 operons, many of which are also regulated by σ
M
, σ
X
, or σ
W
. The σ
V
regulon is strongly and specifically induced by lysozyme, and this induction is key to the intrinsic resistance of
B. subtilis
to lysozyme. Strains with null mutations in either
sigV
or all seven ECF σ factor genes (Δ7ECF) have essentially equal increases in sensitivity to lysozyme. Induction of σ
V
in the Δ7ECF background restores lysozyme resistance, whereas induction of σ
M
, σ
X
, or σ
W
does not. Lysozyme resistance results from the ability of σ
V
to activate the transcription of two operons: the autoregulated
sigV
-
rsiV
-
oatA
-
yrhK
operon and
dltABCDE
. Genetic analyses reveal that
oatA
and
dlt
are largely redundant with respect to lysozyme sensitivity: single mutants are not affected in lysozyme sensitivity, whereas an
oatA dltA
double mutant is as sensitive as a
sigV
null strain. Moreover, the
sigV oatA dltA
triple mutant is no more sensitive than the
oatA dltA
double mutant, indicating that there are no other σ
V
-dependent genes necessary for lysozyme resistance. Thus, we suggest that σ
V
confers lysozyme resistance by the activation of two cell wall modification pathways: O-acetylation of peptidoglycan catalyzed by OatA and
d
-alanylation of teichoic acids by DltABCDE.
Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision
Authors: Orroth Kate K , White Richard G , Freeman Esther E , Bakker Roel , Buvé Anne , Glynn Judith R , Habbema J Dik F , Hayes Richard J 
Published: September 2011

BackgroundA key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities.MethodsA transmission model was fitted to data from the Four Cities Study. Default scenarios included biological cofactor effects on HIV transmission. Counter-factual scenarios were simulated without biological cofactors, with and without higher historical sexual behaviours, and with various rates of male circumcision.ResultsSimulated adult HIV prevalence in 1997 for the default scenarios was 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, in line with data. Without biological cofactors, even implausibly high historical levels of risk behaviour in East Africa could not reproduce the observed heterogeneity in the late 1990s. Increasing the proportion of men circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. Decreasing the proportion circumcised in Yaoundé from 100% to 10% increased HIV prevalence to 26%.ConclusionsDifferences in male circumcision rates are likely to have played a key role in the heterogeneous spread of HIV across Africa. The effect of circumcision interventions can vary depending on the epidemic setting, with a larger effect in more generalised epidemics.
iASPP and Chemoresistance in Ovarian Cancers: Effects on Paclitaxel-Mediated Mitotic Catastrophe
Authors: Jiang LiLi , Siu Michelle K.Y. , Wong Oscar G.W. , Tam Kai-Fai , Lu Xin , Lam Eric W-F. , Ngan Hextan Y.S. , Le Xiao-Feng , Wong Esther S.Y. , Monteiro Lara J. , Chan Hoi-Yan , Cheung Annie N.Y. 
Published: September 2011

AbstractPurpose: iASPP is a specific regulator of p53-mediated apoptosis. Herein, we provided the first report on the expression profile of iASPP in ovarian epithelial tumor and its effect on paclitaxel chemosensitivity.Experimental Design: Expression and amplification status of iASPP was examined in 203 clinical samples and 17 cell lines using immunohistochemistry, quantitative real-time PCR, and immunoblotting, and correlated with clinicopathologic parameters. Changes in proliferation, mitotic catastrophe, apoptosis, and underlying mechanism in ovarian cancer cells of different p53 status following paclitaxel exposure were also analyzed.Results: The protein and mRNA expression of iASPP was found to be significantly increased in ovarian cancer samples and cell lines. High iASPP expression was significantly associated with clear cell carcinoma subtype (P = 0.003), carboplatin and paclitaxel chemoresistance (P = 0.04), shorter overall (P = 0.003), and disease-free (P = 0.001) survival. Multivariate analysis confirmed iASPP expression as an independent prognostic factor. Increased iASPP mRNA expression was significantly correlated with gene amplification (P = 0.023). iASPP overexpression in ovarian cancer cells conferred resistance to paclitaxel by reducing mitotic catastrophe in a p53-independent manner via activation of separase, whereas knockdown of iASPP enhanced paclitaxel-mediated mitotic catastrophe through inactivating separase. Both securin and cyclin B1/CDK1 complex were involved in regulating separase by iASPP. Conversely, overexpressed iASPP inhibited apoptosis in a p53-dependent mode.Conclusions: Our data show an association of iASPP overexpression with gene amplification in ovarian cancer and suggest a role of iASPP in poor patient outcome and chemoresistance, through blocking mitotic catastrophe. iASPP should be explored further as a potential prognostic marker and target for chemotherapy. Clin Cancer Res; 17(21); 6924–33. ©2011 AACR.
The Clinically Active PARP Inhibitor AG014699 Ameliorates Cardiotoxicity but Does Not Enhance the Efficacy of Doxorubicin, despite Improving Tumor Perfusion and Radiation Response in Mice
Authors: Ali Majid , Kamjoo Marzieh , Thomas Huw D. , Kyle Suzanne , Pavlovska Ivanda , Babur Muhammed , Telfer Brian A. , Curtin Nicola J. , Williams Kaye J. 
Published: September 2011

AbstractAG014699 was the first inhibitor of the DNA repair enzyme PARP-1 to enter clinical trial in cancer patients. In addition to enhancing the cytotoxic effect of DNA-damaging chemotherapies, we have previously shown that AG014699 is vasoactive, thereby having the potential to improve drug biodistribution. The effectiveness of the clinical agent doxorubicin is confounded both by poor tumor penetration and cardiotoxicity elicited via PARP hyperactivation. In this study, we analyzed the impact of AG014699 on doxorubicin tolerance and response in breast (MDA-MB-231) and colorectal (SW620, LoVo) tumor models in vitro and in vivo. As anticipated, AG014699 did not potentiate the response to doxorubicin in vitro. In vivo, AG014699 did not influence the pharmacokinetics of doxorubicin; however, it did ameliorate cardiotoxicity. Both toxicity and extent of amelioration were more pronounced in male than in female mice. AG014699 improved vessel perfusion in both MDA-MB-231 and SW620 tumors; however, this neither led to improved tumor-accumulation of doxorubicin nor enhanced therapeutic response. In contrast, when combined with radiotherapy, AG014699 significantly enhanced response both in vitro and in vivo. Real-time assessment of tumor vessel function and companion histologic studies indicate that doxorubicin causes a profound antivascular effect that counters the positive effect of AG014699 on perfusion. These data indicate that although AG014699 can enhance response to some chemotherapeutic drugs via improved delivery, this does not apply to doxorubicin. PARP inhibitors may still be of use to counter doxorubicin toxicity, and if the gender effect translates from rodents to humans, this would have greater effect in males. Mol Cancer Ther; 10(12); 2320–9. ©2011 AACR.
PET Imaging May Provide a Novel Biomarker and Understanding of Right Ventricular Dysfunction in Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Bokhari Sabahat , Raina Amresh , Berman Rosenweig Erika , Schulze P. Christian , Bokhari Justin , Einstein Andrew J. , Barst Robyn J. , Johnson Lynne L. 
Published: September 2011

Background—
The clinical course in pulmonary arterial hypertension (PAH) is variable, and there is limited information on the determinants and progression of right ventricular (RV) dysfunction. The objective is to develop PET metabolic imaging of the RV as a noninvasive tool in patients with PAH.

Methods and Results—

We performed PET scanning in 16 patients with idiopathic PAH (age, 41±14 years, 82% women) using
13
N-NH
3
for perfusion imaging and
18
F-fluorodeoxyglucose for metabolic imaging. The myocardium was divided into 6 regions of interest (3 left ventricular [LV], 3 RV), and time-activity curves were generated. A 2- compartment model was used to calculate myocardial blood flow (MBF), and Patlak analysis was used to calculate the rate of myocardial glucose uptake (MGU). All patients underwent cardiac catheterization, cardiac MRI, and cardiopulmonary exercise testing with gas exchange. MBF, MGU, and the ratio of RV/LV MGU were correlated to clinical parameters. Pulmonary artery (PA) pressure was 79±19/30±8 mm Hg (mean, 48±10 mm Hg). MBF was 0.84±0.33 mL/g per minute for the LV and 0.45±0.14 mL/g per minute for the RV. Mean MGU was 136±72 nmol/g per minute for the LV and 96±69 nmol/g per minute for the RV. The ratio of RV/LV MGU correlated significantly with PA systolic (
r
=0.75,
P
=0.0085) and mean (
r
=0.87,
P
=0.001) pressure and marginally with maximum oxygen consumption (
r
=−0.59,
P
=0.05). RV free wall MGU also correlated well with mean PA pressure (
r
=0.66,
P
=0.03).

Conclusions—

PET scanning with
13
N-NH
3
and
18
F-fluorodeoxyglucose is a feasible modality for quantifying RV blood flow and metabolism in patients with idiopathic PAH.
Physical and Cognitive Effects of Virtual Reality Integrated Training
Authors: Stone Richard T. , Watts Kristopher P. , Zhong Peihan , Wei Chen-Shuang 
Published: September 2011

Objective: The objective of this study was to evaluate the cognitive and physical impact of virtual reality (VR) integrated training versus traditional training methods in the domain of weld training. Background: Weld training is very important in various industries and represents a complex skill set appropriate for advanced training intervention. As such, there has been a long search for the most successful and most cost-effective method for training new welders. Method: Participants in this study were randomly assigned to one of two separate training courses taught by sanctioned American Welding Society certified welding instructors; the duration of each course was 2 weeks. After completing the training for a specific weld type, participants were given the opportunity to test for the corresponding certification. Participants were evaluated in terms of their cognitive and physical parameters, total training time exposure, and welding certification awards earned. Each of the four weld types taught in this study represented distinct levels of difficulty and required the development of specialized knowledge and skills. Results: This study demonstrated that participants in the VR integrated training group (VR50) performed as well as, and in some cases, significantly outperformed, the traditional welding (TW) training group. The VR50 group was found to have a 41.6% increase in overall certifications earned compared with the TW group. Conclusion: VR technology is a valuable tool for the production of skilled welders in a shorter time and often with more highly developed skills than their traditionally trained counterparts. Application: These findings strongly support the use of VR integrated training in the welding industry.
Shining New Light on the Hawthorne Illumination Experiments
Authors: Izawa Masumi R. , French Michael D. , Hedge Alan 
Published: September 2011

Objective: This study provides an historical and statistical analysis of archival data from the Hawthorne illumination experiments. Background: Previous accounts of the illumination experiments are fraught with inconsistencies because they have been based on secondary sources. The general consensus has been that variations in light levels had no effect on worker productivity at Hawthorne. All reports and data were thought to have been destroyed, but an archive at Cornell University was found to contain copies of the original documentation and much of the data from all three illumination experiments. Conclusions were originally drawn from visual comparisons of productivity graphs, and the data have never been properly statistically analyzed. Method: Archival reports, notes, photographs, and letters on the experiments were consulted. Productivity data were extracted from the tables and graphs in the reports and statistically analyzed for each experiment. Results: Previously unpublished details of the illumination experiments emerged. An effect of lighting on productivity was found in the first treatment sequence for the first experiment, but this finding was not confirmed in the second sequence or in the second and third experiments. Conclusion: Experimental results provided inconsistent evidence of an association between light levels and productivity. All three experiments were found to be seriously flawed. Application: This study challenges popular accounts of the “Hawthorne effect,” and the shortcomings of these experiments also have implications for the design of field studies.
Biomechanical Effects of Mobile Computer Location in a Vehicle Cab
Authors: Saginus Kyle A. , Marklin Richard W. , Seeley Patricia , Simoneau Guy G. , Freier Stephen 
Published: September 2011

Objective: The objective of this research is to determine the best location to place a conventional mobile computer supported by a commercially available mount in a light truck cab. Background: U.S. and Canadian electric utility companies are in the process of integrating mobile computers into their fleet vehicle cabs. There are no publications on the effect of mobile computer location in a vehicle cab on biomechanical loading, performance, and subjective assessment. Method: The authors tested four locations of mobile computers in a light truck cab in a laboratory study to determine how location affected muscle activity of the lower back and shoulders; joint angles of the shoulders, elbows, and wrist; user performance; and subjective assessment. A total of 22 participants were tested in this study. Results: Placing the mobile computer closer to the steering wheel reduced low back and shoulder muscle activity. Joint angles of the shoulders, elbows, and wrists were also closer to neutral angle. Biomechanical modeling revealed substantially less spinal compression and trunk muscle force. In general, there were no practical differences in performance between the locations. Subjective assessment indicated that users preferred the mobile computer to be as close as possible to the steering wheel. Conclusion: Locating the mobile computer close to the steering wheel reduces risk of injuries, such as low back pain and shoulder tendonitis. Application: Results from the study can guide electric utility companies in the installation of mobile computers into vehicle cabs. Results may also be generalized to other industries that use trucklike vehicles, such as construction.
Predictors of Computer Use in Community-Dwelling, Ethnically Diverse Older Adults
Authors: Werner Julie M. , Carlson Mike , Jordan-Marsh Maryalice , Clark Florence 
Published: September 2011

Objective: In this study, we analyzed self-reported computer use, demographic variables, psychosocial variables, and health and well-being variables collected from 460 ethnically diverse, community-dwelling elders to investigate the relationship computer use has with demographics, well-being, and other key psychosocial variables in older adults. Background: Although younger elders with more education, those who employ active coping strategies, or those who are low in anxiety levels are thought to use computers at higher rates than do others, previous research has produced mixed or inconclusive results regarding ethnic, gender, and psychological factors or has concentrated on computer-specific psychological factors only (e.g., computer anxiety). Few such studies have employed large sample sizes or have focused on ethnically diverse populations of community-dwelling elders. Method: With a large number of overlapping predictors, zero-order analysis alone is poorly equipped to identify variables that are independently associated with computer use. Accordingly, both zero-order and stepwise logistic regression analyses were conducted to determine the correlates of two types of computer use: e-mail and general computer use. Results: Results indicate that younger age, greater level of education, non-Hispanic ethnicity, behaviorally active coping style, general physical health, and role-related emotional health each independently predicted computer usage. Conclusion: Study findings highlight differences in computer usage, especially in regard to Hispanic ethnicity and specific health and well-being factors. Application: Potential applications of this research include future intervention studies, individualized computer-based activity programming, or customizable software and user interface design for older adults responsive to a variety of personal characteristics and capabilities.