bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Design of an Artificial Genetic Switch: Co-Option of the H-NS-Repressed
proU
Operon by the VirB Virulence Master Regulator
Authors: Kane Kelly A. , Dorman Charles J. 
Published: August 2011

ABSTRACT

The H-NS protein represses the transcription of hundreds of genes in Gram-negative bacteria. Derepression is achieved by a multitude of mechanisms, many of which involve the binding of a protein to DNA at the repressed promoter in a manner that compromises the maintenance of the H-NS–DNA nucleoprotein repression complex. The principal virulence gene promoters in
Shigella flexneri
, the cause of bacillary dysentery, are repressed by H-NS. VirB, a protein that closely resembles members of the ParB family of plasmid-partitioning proteins, derepresses the operons that encode the main structural components and the effector proteins of the
S. flexneri
type III secretion system. Bioinformatic analysis suggests that VirB has been co-opted into its current role as an H-NS antagonist in
S. flexneri
. To test this hypothesis, the potential for VirB to act as a positive regulator of
proU
, an operon that is repressed by H-NS, was assessed. Although VirB has no known relationship with the osmoregulated
proU
operon, it could relieve H-NS-mediated repression when the
parS
-like VirB binding site was placed appropriately upstream of the RpoD-dependent
proU
promoter. These results reveal the remarkable facility with which novel regulatory circuits can evolve, at least among those promoters that are repressed by H-NS.
Effects on Transcription of Mutations in
ygjD
,
yeaZ
, and
yjeE
Genes, Which Are Involved in a Universal tRNA Modification in Escherichia coli
Authors: Hashimoto Chika , Sakaguchi Kohei , Taniguchi Yuko , Honda Hirofumi , Oshima Taku , Ogasawara Naotake , Kato Jun-ichi 
Published: August 2011

ABSTRACT

The
Escherichia coli ygjD
gene is critical for the universal tRNA modification
N
6
-threonylcarbamoyladenosine, together with two other essential genes,
yeaZ
and
yjeE
. This study showed that the transcription of the
thr
and
ilv
operons in
ygjD
mutants was increased through the inhibition of transcription attenuation and that
dnaG
transcription was reduced.
Mutational and Phylogenetic Analyses of the Mycobacterial
mbt
Gene Cluster
Authors: Chavadi Sivagami Sundaram , Stirrett Karen L. , Edupuganti Uthamaphani R. , Vergnolle Olivia , Sadhanandan Gigani , Marchiano Emily , Martin Che , Qiu Wei-Gang , Soll Clifford E. , Quadri Luis E. N. 
Published: August 2011

ABSTRACT

The mycobactin siderophore system is present in many
Mycobacterium
species, including
M. tuberculosis
and other clinically relevant mycobacteria. This siderophore system is believed to be utilized by both pathogenic and nonpathogenic mycobacteria for iron acquisition in both
in vivo
and
ex vivo
iron-limiting environments, respectively. Several
M. tuberculosis
genes located in a so-called
mbt
gene cluster have been predicted to be required for the biosynthesis of the core scaffold of mycobactin based on sequence analysis. A systematic and controlled mutational analysis probing the hypothesized essential nature of each of these genes for mycobactin production has been lacking. The degree of conservation of
mbt
gene cluster orthologs remains to be investigated as well. In this study, we sought to conclusively establish whether each of nine
mbt
genes was required for mycobactin production and to examine the conservation of gene clusters orthologous to the
M. tuberculosis
mbt
gene cluster in other bacteria. We report a systematic mutational analysis of the
mbt
gene cluster ortholog found in
Mycobacterium smegmatis
. This mutational analysis demonstrates that eight of the nine
mbt
genes investigated are essential for mycobactin production. Our genome mining and phylogenetic analyses reveal the presence of orthologous
mbt
gene clusters in several bacterial species. These gene clusters display significant organizational differences originating from an intricate evolutionary path that might have included horizontal gene transfers. Altogether, the findings reported herein advance our understanding of the genetic requirements for the biosynthesis of an important mycobacterial secondary metabolite with relevance to virulence.
Expression during Host Infection and Localization of Yersinia pestis Autotransporter Proteins
Authors: Lenz Jonathan D. , Lawrenz Matthew B. , Cotter David G. , Lane M. Chelsea , Gonzalez Rodrigo J. , Palacios Michelle , Miller Virginia L. 
Published: August 2011

ABSTRACTYersinia pestisCO92 has 12 open reading frames encoding putative conventional autotransporters (yaps), nine of which appear to produce functional proteins. Here, we demonstrate the ability of the Yap proteins to localize to the cell surface of bothEscherichia coliandYersinia pestisand show that a subset of these proteins undergoes processing by bacterial surface omptins to be released into the supernatant. Numerous autotransporters have been implicated in pathogenesis, suggesting a role for the Yaps as virulence factors inY. pestis. Using the C57BL/6 mouse models of bubonic and pneumonic plague, we determined that all of these genes are transcribed in the lymph nodes during bubonic infection and in the lungs during pneumonic infection, suggesting a role for the Yaps during mammalian infection.In vitrotranscription studies did not identify a particular environmental stimulus responsible for transcriptional induction. The primary sequences of the Yaps reveal little similarity to any characterized autotransporters; however, two of the genes are present in operons, suggesting that the proteins encoded in these operons may function together. Further work aims to elucidate the specific functions of the Yaps and clarify the contributions of these proteins toY. pestispathogenesis.
Overall patient satisfaction with hospitals: effects of patient-reported experiences and fulfilment of expectations
Authors: Bjertnaes Oyvind A , Sjetne Ingeborg Strømseng , Iversen Hilde Hestad 
Published: August 2011

BackgroundPatient satisfaction and experiences are important parts of healthcare quality, but patient expectations are seldom included in quality assessments. The objective of this study was to estimate the effects of different predictors of overall patient satisfaction with hospitals, including patient-reported experiences, fulfilment of patient expectations and socio-demographic variables.MethodsData were collected using a national patient-experience survey of 63 hospitals in the five health regions in Norway during the autumn of 2006. Postal questionnaires were mailed to 24 141 patients after their discharge from hospital. Non-respondents were sent a reminder after 4 weeks. Multivariate linear regression analysis including multilevel regression was used to assess the predictors of overall patient satisfaction with hospitals.ResultsThirteen variables were significantly associated with overall patient satisfaction: two variables about fulfilment of expectations, eight about patient-reported experiences and three socio-demographic variables. The regression model explained 59% of the variation in overall patient satisfaction. The most important predictor of patient satisfaction with hospitals was patient-reported experiences with the nursing services (β=0.27, p<0.001), followed by fulfilment of patient expectations (β=0.21, p<0.001), experiences with doctor services (β=0.12, p<0.001) and perceived incorrect treatment (β=−0.12, p<0.001). Multilevel regression analysis confirmed most of the findings, but revealed that age was not a significant predictor of overall patient satisfaction.ConclusionsThe study showed that both fulfilment of expectations and patient-reported experiences are distinct from but related to overall patient satisfaction. The most important predictors for overall patient satisfaction with hospitals are patient-reported experiences and fulfilment of expectations.
Oncology professionals' views on the use of antidepressants in cancer patients: a qualitative interview study
Authors: Holch Patricia , Absolom Kate L , Pini Simon , Hill Kate M , Liu Alan , Sharpe Michael , Richardson Alison , Hosker Christian , Velikova Galina 
Published: August 2011

ObjectivesEmotional distress, including depression, is an important issue for cancer patients and their families. Guidelines recommend the use of antidepressant drugs (ADs) for the management of depression in cancer. This study explores the views of oncology professionals about the inclusion of ADs in treatment plans.DesignSemi-structured interview study. Data were analysed using framework analysis.SettingA specialist cancer centre and six district general hospitals across the Yorkshire Cancer Network.Participants18 randomly selected professionals from lung, breast, urology and colorectal cancer teams: oncologists (n=8), surgeons (n=3), clinical nurse specialists (n=2) and ward nurses (n=5).ResultsThree main themes emerged relating to professionals' attitudes, knowledge and behaviour. Positive attitudes were primarily expressed by nurses. However, negative views were expressed about the potential for over-reliance on ADs, and their use constituting ‘giving in’. Doctors reported a lack of confidence in the use of and knowledge about ADs with an associated reluctance to prescribe. The general practitioner (GP) was regarded as the most appropriate professional to prescribe ADs.ConclusionsCancer professionals highlighted a need for training in the appropriate use of ADs. Further, this research suggests that negative attitudes towards antidepressants may be a factor in their exclusion from treatment plans. The GP is seen to have a key prescribing role for AD therapy; however, it is unclear whether the GPs is asked to do this. This research raises questions about the adequacy of ADs in cancer care and to what extent the GP is able to meet this need.
Remifentanil use in emergency department patients: initial experience
Authors: Sacchetti Alfred , Jachowski Jennifer , Heisler Josephine , Cortese Teena 
Published: August 2011

IntroductionThis study examines the use of remifentanil, an ultra-short-acting opioid, in emergency department (ED) patients.MethodsChart review of ED patients receiving remifentanil for procedural sedation in an urban general ED.Results50 patients over a 28-month period with a mean age of 30.6 years (±2.6) were reviewed. Procedures performed included: abscess drainage (13); fracture care (9); thoracostomy (8); lumbar puncture (7); shoulder reduction (3); cardioversion (3) and others (7). Six (12%) cases received additional rescue medications. All procedures were successfully completed in the ED. No complications were recorded but 21 (42%) were admitted for underlying pathology.ConclusionRemifentanil is a safe and effective medication for ED use.
Knowledge of radiation exposure in common radiological investigations: a comparison between radiologists and non-radiologists
Authors: Lee Ryan K L , Chu Winnie C W , Graham Colin A , Rainer Timothy H , Ahuja Anil T 
Published: August 2011

BackgroundRadiological examinations are commonly requested for patients to aid clinical diagnosis. However, many doctors do not realise how much radiation dosage their patients are exposed to during radiological investigations. This study aims to assess and compare the knowledge of radiologists and non-radiologists about radiation doses of common radiological investigations.MethodsA prospective questionnaire study of doctors about the dosage of commonly performed radiological investigations in a university teaching hospital in Hong Kong. Participants were asked to indicate the average dose of radiation (in mSv) for a standard chest x-ray exposure. Doctors were then asked to estimate the doses of radiation (measured in chest x-ray equivalents) for various radiological procedures. The results of radiologists and non-radiologists were compared.Results158 doctors (25 radiologists and 133 non-radiologists) completed the questionnaire. The overall accuracy was 40% for radiologists and 16% for non-radiologists. One-third of non-radiologists could not distinguish radiological examinations with or without ionising radiation. No non-radiologists correctly stated the radiation dose (in mSv) of a conventional chest x-ray, and 77% underestimated the dose of radiological examinations. For radiologists, only 32% were correct for the radiation dose of a conventional chest x-ray while 7% underestimated the radiation doses.ConclusionKnowledge of radiation doses of investigation is generally inadequate among radiologists, and particularly poor in non-radiologists. Underestimation of radiation doses may expose patients to increasing radiological investigation and exposure to radiation hazards. Awareness of the radiation hazard of radiological examinations should be raised among medical professionals.
Hemiparasite – host plant interactions and the impact of herbivory: a field experiment
Authors: Van Hoveln Mickayla D. , Evans Bethany A. , Borowicz Victoria A. 
Published: August 2011

Schizachyrium scoparium Michx. (Nash) growing naturally with varying numbers of the perennial hemiparasite Pedicularis canadensis L. were randomly assigned to one of four clipping treatments (none, early, late, early and late) to determine how parasitism and herbivory affect the grass and whether herbivory of the host indirectly affects hemiparasite growth. Any clipping eliminated subsequent flowering by S. scoparium in year 1 and reduced the number of plants that flowered in year 2, when no clipping occurred. Only hosts clipped early exhibited depressed growth after one summer. The following year plants that had been clipped twice the previous year produced the least shoot mass, and plants that were never clipped produced the most. Hemiparasite load was negatively associated with host shoot mass, especially in year 1, but did not alter the host’s compensatory response to clipping. The effects of host size and host clipping on the nearest hemiparasite were determined in year 1. Pedicularis canadensis shoot mass declined with host size if the host was clipped late, but increased with host size when clipping occurred once early in the season. Although the impact of hemiparasites and clipping on host growth are independent, clipping can alter the value of the host for parasites.
Dicer-Mediated Upregulation of BCRP Confers Tamoxifen Resistance in Human Breast Cancer Cells
Authors: Selever Jennifer , Gu Guowei , Lewis Michael T. , Beyer Amanda , Herynk Matthew H. , Covington Kyle R. , Tsimelzon Anna , Dontu Gabriela , Provost Patrick , Di Pietro Attilio , Boumendjel Ahcène , Albain Kathy , Miele Lucio , Weiss Heidi , Barone Ines , Ando Sebastiano , Fuqua Suzanne A. W. 
Published: August 2011

Abstract
Purpose: Tamoxifen (Tam) is the most prescribed hormonal agent for treatment of estrogen receptor α (ERα)-positive breast cancer patients. Using microarray analysis, we observed that metastatic breast tumors resistant to Tam therapy had elevated levels of Dicer.
Experimental Design: We overexpressed Dicer in ERα-positive MCF-7 human breast cancer cells and observed a concomitant increase in expression of the breast cancer resistance protein (BCRP). We thus hypothesized that Tam resistance associated with Dicer overexpression in ERα-positive breast cancer cells may involve BCRP. We analyzed BCRP function in Dicer-overexpressing cells using growth in soft agar and mammosphere formation and evaluated intracellular Tam efflux.
Results: In the presence of Tam, Dicer-overexpressing cells formed resistant colonies in soft agar, and treatment with BCRP inhibitors restored Tam sensitivity. Tumor xenograft studies confirmed that Dicer-overexpressing cells were resistant to Tam in vivo. Tumors and distant metastases could be initiated with as few as five mammosphere cells from both vector and Dicer-overexpressing cells, indicating that the mammosphere assay selected for cells with enhanced tumor-initiating and metastatic capacity. Dicer-overexpressing cells with elevated levels of BCRP effluxed Tam more efficiently than control cells, and BCRP inhibitors were able to inhibit efflux.
Conclusion: Dicer-overexpressing breast cancer cells enriched for cells with enhanced BCRP function. We hypothesize that it is this population which may be involved in the emergence of Tam-resistant growth. BCRP may be a novel clinical target to restore Tam sensitivity. Clin Cancer Res; 17(20); 6510–21. ©2011 AACR.
Psychological distress in Canada: The role of employment and reasons of non-employment
Authors: Marchand Alain , Drapeau Aline , Beaulieu-Prévost Dominic 
Published: August 2011

Background: This study investigated variations in psychological distress in a large sample of the Canadian population according to employment status, occupation, work organization conditions, reasons for non-employment, stress and support outside the work environment, family situation and individual characteristics. Methods: Data came from cycle 4 (2000–1) of the Canadian National Population Health Survey conducted by Statistics Canada. Multiple regression analyses, adjusted for the family situation, the level of support from the social network and the individual characteristics, were carried out on a sample of 7258 individuals aged from 18 to 65 years. Results: Occupation, social support at work, age, self-esteem, presence of children aged five and under and social support outside of the workplace were associated with lower levels of psychological distress, while permanent and temporary disability, psychological demands in the workplace, job insecurity, female gender, and stressful financial, marital and parental situations were related to higher levels of psychological distress. Conclusions: Findings from this study suggest that, in terms of psychological distress, having a job is not always better than non-employment, and that specific non-employment situations associate differently with psychological distress.
Comparative study of the experience of caregiving in bipolar affective disorder and schizophrenia
Authors: Grover Sandeep , Chakrabarti Subho , Aggarwal Munish , Avasthi Ajit , Kulhara Parmanand , Sharma Sunil , Khehra Nitasha 
Published: August 2011

Background: Bipolar affective disorder and schizophrenia are disabling illnesses and place a considerable degree of burden on the caregivers. Many studies from India have measured the burden of care in schizophrenia and some studies have measured the burden experienced by the caregivers of bipolar affective disorder. Few studies have compared this variable in these disorders. Experience of caregiving is a broader concept that takes into consideration both the negative and positive appraisal of the caregiving. However, no study from India has compared the experience of caregiving in bipolar affective disorder and schizophrenia. Aim of the study: To study the experience of caregiving in a group of caregivers of bipolar patients and compare the same with caregivers of patients with schizophrenia. Method: Seventy patients with a diagnosis of bipolar affective disorder and 70 with a diagnosis of schizophrenia were selected for the present study. Patients were assessed on the Hamilton Depression Rating Scale, the Young Mania Rating Scale and the Positive and Negative Syndrome Scale depending upon their diagnosis. They were also assessed on the Global Assessment of Functioning (GAF) scale. Caregivers of the patients were assessed on the General Health Questionnaire (GHQ) and the Experience of Caregiving Inventory (ECI). Results: The maximum ECI score was seen in the domain of handling ‘difficult behaviour’ in both the groups. Compared to caregivers of patients with bipolar affective disorder, caregivers of patients with schizophrenia had overall more positive and negative appraisal of caregiving experience while caring for their ill relatives. The difference reached significant levels for all domains but for the domains of ‘effects on family’, ‘need for back-up’ and ‘good aspect of relationship’. There were significant differences too for the total positive personal experience sub-score. There was a significant positive correlation between the negative and positive caregiving experience score for both schizophrenia and bipolar groups. Conclusion: The caregivers of both bipolar affective disorder and schizophrenia appraise the caregiving negatively, while at the same time appraising some positive aspects of it. Caregivers of schizophrenia patients appraise caregiving more negatively than those of bipolar affective disorder patients.
Hepcidin regulation by innate immune and infectious stimuli
Authors: Armitage Andrew E. , Eddowes Lucy A. , Gileadi Uzi , Cole Suzanne , Spottiswoode Natasha , Selvakumar Tharini Ashtalakshmi , Ho Ling-Pei , Townsend Alain R. M. , Drakesmith Hal 
Published: August 2011

Abstract
Hepcidin controls the levels and distribution of iron, an element whose availability can influence the outcome of infections. We investigated hepcidin regulation by infection-associated cytokines, pathogen-derived molecules, and whole pathogens in vitro and in vivo. We found that IL-22, an effector cytokine implicated in responses to extracellular infections, caused IL-6–independent hepcidin up-regulation in human hepatoma cells, suggesting it might represent an additional inflammatory hepcidin agonist. Like IL-6, IL-22 caused phosphorylation of STAT3 and synergized with BMP6 potentiating hepcidin induction. In human leukocytes, IL-6 caused potent, transient hepcidin up-regulation that was augmented by TGF-β1. Pathogen-derived TLR agonists also stimulated hepcidin, most notably the TLR5 agonist flagellin in an IL-6–dependent manner. In contrast, leukocyte hepcidin induction by heat-killed Candida albicans hyphae was IL-6–independent, but partially TGF-β–dependent. In a murine acute systemic candidiasis model, C albicans strongly stimulated hepcidin, accompanied by a major reduction in transferrin saturation. Similarly, hepcidin was up-regulated with concomitant lowering of serum iron during acute murine Influenza A/PR/8/34 virus (H1N1) infection. This intracellular pathogen also stimulated hepcidin expression in leukocytes and hepatoma cells. Together, these results indicate that hepcidin induction represents a component of the innate immune response to acute infection, with the potential to affect disease pathogenesis.
TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals
Authors: Nai Antonella , Pagani Alessia , Silvestri Laura , Campostrini Natascia , Corbella Michela , Girelli Domenico , Traglia Michela , Toniolo Daniela , Camaschella Clara 
Published: August 2011

Abstract
The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene. Cleaving the bone morphogenetic protein (BMP) coreceptor hemojuvelin (HJV), MT2 impairs the BMP/son of mothers against decapentaplegic homologs (SMAD) signaling pathway, down-regulates hepcidin, and facilitates iron absorption. TMPRSS6 inactivation causes iron-deficiency anemia refractory to iron administration both in humans and mice. Genome-wide association studies have shown that the SNP rs855791, which causes the MT2 V736A amino acid substitution, is associated with variations of serum iron, transferrin saturation, hemoglobin, and erythrocyte traits. In the present study, we show that, in vitro, MT2 736A inhibits hepcidin more efficiently than 736V. Moreover, in a genotyped population, after exclusion of samples with iron deficiency and inflammation, hepcidin, hepcidin/transferrin saturation, and hepcidin/ferritin ratios were significantly lower and iron parameters were consistently higher in homozygotes 736A than in 736V. Our results indicate that rs855791 is a TMPRSS6 functional variant and strengthen the idea that even a partial inability to modulate hepcidin influences iron parameters and, indirectly, erythropoiesis.