bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-Binding Protein Khd1 and Ccr4 Deadenylase Play Overlapping Roles in the Cell Wall Integrity Pathway in Saccharomyces cerevisiae
Authors: Ito Wataru , Li Xia , Irie Kaoru , Mizuno Tomoaki , Irie Kenji
Published: August 2011

The
Saccharomyces cerevisiae
RNA-binding protein Khd1/Hek2 associates with hundreds of potential mRNA targets preferentially, including the mRNAs encoding proteins localized to the cell wall and plasma membrane. We have previously revealed that Khd1 positively regulates expression of
MTL1
mRNA encoding a membrane sensor in the cell wall integrity (CWI) pathway. However, a
khd1
Δ mutation has no detectable phenotype on cell wall synthesis. Here we show that the
khd1
Δ mutation causes a severe cell lysis when combined with the deletion of the
CCR4
gene encoding a cytoplasmic deadenylase. We identified the
ROM2
mRNA, encoding a guanine nucleotide exchange factor (GEF) for Rho1, as a target for Khd1 and Ccr4. The
ROM2
mRNA level was decreased in the
khd1
Δ
ccr4
Δ mutant, and
ROM2
overexpression suppressed the cell lysis of the
khd1
Δ
ccr4
Δ mutant. We also found that Ccr4 negatively regulates expression of the
LRG1
mRNA encoding a GTPase-activating protein (GAP) for Rho1. The
LRG1
mRNA level was increased in the
ccr4
Δ and
khd1
Δ
ccr4
Δ mutants, and deletion of
LRG1
suppressed the cell lysis of the
khd1
Δ
ccr4
Δ mutant. Our results presented here suggest that Khd1 and Ccr4 modulate a signal from Rho1 in the CWI pathway by regulating the expression of RhoGEF and RhoGAP.
XoxF Is Required for Expression of Methanol Dehydrogenase in Methylobacterium extorquens AM1
Authors: Skovran Elizabeth , Palmer Alexander D. , Rountree Austin M. , Good Nathan M. , Lidstrom Mary E.
Published: August 2011

In Gram-negative methylotrophic bacteria, the first step in methylotrophic growth is the oxidation of methanol to formaldehyde in the periplasm by methanol dehydrogenase. In most organisms studied to date, this enzyme consists of the MxaF and MxaI proteins, which make up the large and small subunits of this heterotetrameric enzyme. The
Methylobacterium extorquens
AM1 genome contains two homologs of MxaF, XoxF1 and XoxF2, which are ∼50% identical to MxaF and ∼90% identical to each other. It was previously reported that
xoxF
is not required for methanol growth in
M. extorquens
AM1, but here we show that when both
xoxF
homologs are absent, strains are unable to grow in methanol medium and lack methanol dehydrogenase activity. We demonstrate that these defects result from the loss of gene expression from the
mxa
promoter and suggest that XoxF is part of a complex regulatory cascade involving the 2-component systems MxcQE and MxbDM, which are required for the expression of the methanol dehydrogenase genes.
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

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

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

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

Yersinia 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

Background

Patient 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.

Methods

Data 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.

Results

Thirteen 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.

Conclusions

The 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

Objectives

Emotional 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.

Design

Semi-structured interview study. Data were analysed using framework analysis.

Setting

A specialist cancer centre and six district general hospitals across the Yorkshire Cancer Network.

Participants

18 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).

Results

Three 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.

Conclusions

Cancer 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

Introduction

This study examines the use of remifentanil, an ultra-short-acting opioid, in emergency department (ED) patients.

Methods

Chart review of ED patients receiving remifentanil for procedural sedation in an urban general ED.

Results

50 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.

Conclusion

Remifentanil 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

Background

Radiological 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.

Methods

A 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.

Results

158 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.

Conclusion

Knowledge 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.
Ins and outs of implementing a pet health plan
Authors: Goulding John
Published: August 2011

The number of pet health plans delivered by veterinary surgeons has increased significantly over the past 10 years in both small animal and equine practice. They offer many benefits for both the client and the practice, but require careful planning if they are to be implemented successfully. In this article, John Goulding provides an overview of the benefits and difficulties associated with setting up and running a health plan, and describes some of the common models available.
Critical care of the rabbit
Authors: Hedley Joanna
Published: August 2011

Although rabbits are an increasingly popular household pet, they still retain their wild instincts. From the veterinary surgeon's point of view, the most important of these is the tendency of rabbits to hide signs of illness – critical for the survival of a prey species, but unhelpful in a consulting room. Consequently, any rabbit noticed as being ‘sick’ by an owner is often a much more critical patient than a dog or cat with similar problems. This article describes the steps that must be taken when a critically ill rabbit is presented for treatment, and provides some examples of the type of emergency cases that might be seen.
Digital signage for the practice waiting room
Authors: Barrand Keith
Published: August 2011

Digital signage is a form of dynamic communication that generally comprises replaying digital media as slideshows and short films on digital display screens such as TVs, touch screens or projectors in public venues. It can be used for advertising, education or to provide information and, nowadays, is seen everywhere – from estate agents' windows to doctors' surgeries to shopping centres. This has been driven primarily by the falling price of digital screens. In this article, Keith Barrand describes the practical aspects of setting up and running simple digital signage in the practice waiting room, and suggests how to make your content relevant, lively and interesting.
Customer focus: understanding client needs and motivations
Authors: Lowndes Philip
Published: August 2011

Although it is difficult to second guess why people do things, it is possible to model why they do them and then use this to make sure that your practice is best placed to attract and retain clientele. In this article, Philip Lowndes describes a simple model comprising six motivations that are exhibited by people to differing degrees that can be used to attract customers to your practice.
Practical assessment of blood smears in dogs and cats
Authors: Wilson Rand
Published: August 2011

Complete blood count (CBC) or haematological analysis is an integral part of the diagnostic work‐up in dogs and cats, and involves assessment of a freshly prepared blood smear (also known as a blood film). Despite the widespread availability of automated analysers, the value of a basic blood smear should not be forgotten and should be incorporated into routine blood testing in clinical practice. This article describes a step‐by‐step approach to blood smear evaluation, which is simple, inexpensive and quick to perform.
Various endovascular approaches to the management of free floating carotid thrombi: a technical report
Authors: Park Jee Won , Lee Deok Hee , Choi Choong Gon , Kim Sang Joon , Suh Dae Chul
Published: August 2011

Ischemic strokes are seldom caused by free floating thrombi (FFTs) in the carotid artery. Because FFTs are fairly uncommon and their pathophysiology has not yet been clarified, no definite management guidelines have been established. Four consecutive patients with FFTs in the internal and/or common carotid artery are described. These patients were successfully treated by various endovascular treatment methods.
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.
ASYMMETRIC TRANSITION AND TIME-SCALE SEPARATION IN INTERLINKED POSITIVE FEEDBACK LOOPS
Authors: YORDANOV PENCHO , TYANOVA STEFKA , HÜTT MARC-THORSTEN , LESNE ANNICK
Published: August 2011

In [Brandman et al., 2005] it was proposed that interlinked fast and slow positive feedback loops are a frequent motif in biological signaling, because such a device can allow for a rapid response to an external stimulus (sensitivity) along with a certain noise-buffering capacity (robustness), as soon as the two loops operate on different time scales. Here we explore the properties of the nonlinear system responsible for this behavior. We argue that (a) the noise buffering is not linked to the stochastic nature of the stimulus, but only to the time scale of the stimulus variation compared to the intrinsic time scales of the system, and (b) this buffering of stimulus variations follows from the stabilization of a region of the state space away from the equilibrium branches of the system. Our analysis is based on a slow-fast decomposition of the dynamics. We analyze the strength of this buffering as a function of the time scales involved and the Boolean logic of the coupling between dynamic variables, as well as of the amplitude of the stimulus variations. We underline that such a nonequilibrium regime is universal as soon as the stimulus time scale is smaller than the larger time scale of the system, preventing the prediction of the behavior from the features of the bifurcation diagram or using a linear analysis.
Cardiac overexpression of 8-oxoguanine DNA glycosylase 1 protects mitochondrial DNA and reduces cardiac fibrosis following transaortic constriction
Authors: Wang Jianxun , Wang Qianwen , Watson Lewis J. , Jones Steven P. , Epstein Paul N.
Published: August 2011

Cardiac failure is associated with increased levels of oxidized DNA, especially mitochondrial (mtDNA). It is not known if oxidized mtDNA contributes to cardiac dysfunction. To test if protection of mtDNA can reduce cardiac injury, we produced transgenic mice with cardiomyocyte-specific overexpression of the DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) isoform 2a. In one line of mice, the transgene increased OGG1 activity by 115% in mitochondria and by 28% in nuclei. OGG1 transgenic mice demonstrated significantly lower cardiac mitochondrial levels of the DNA guanine oxidation product 7,8-dihydro-8-oxoguanine (8-oxo-dG) under basal conditions, after doxorubicin administration, or after transaortic constriction (TAC), but the transgene produced no detectable reduction in nuclear 8-oxo-dG content. OGG1 mice were tested for protection from the cardiac effects of TAC 13 wk after surgery. Compared with FVB-TAC mice, hearts from OGG1-TAC mice had lower levels of β-myosin heavy chain mRNA but they did not display significant differences in the ratio of heart weight to tibia length or protection of cardiac function measured by echocardiography. The principle benefit of OGG1 overexpression was a significant decrease in TAC-induced cardiac fibrosis. This protection was indicated by reduced Sirius red staining on OGG1 cardiac sections and by significantly decreased induction of collagen 1 and 3 mRNA expression in OGG1 hearts after TAC surgery. These results provide a new model to assess the damaging cardiac effects of 8-oxo-dG formation and suggest that increased repair of 8-oxo-dG in mtDNA decreases cardiac pathology.
Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization mediate exercise intolerance in Barth syndrome
Authors: Spencer Carolyn T. , Byrne Barry J. , Bryant Randall M. , Margossian Renee , Maisenbacher Melissa , Breitenger Petar , Benni Paul B. , Redfearn Sharon , Marcus Edward , Cade W. Todd
Published: August 2011

Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O2 extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O2 extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O2 extraction. Adjusting for age, peak O2 consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg−1·min−1, P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O2 saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: −5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.
Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension
Authors: Pojoga Luminita H. , Williams Jonathan S. , Yao Tham M. , Kumar Abhinav , Raffetto Joseph D. , do Nascimento Graciliano R. A. , Reslan Ossama M. , Adler Gail K. , Williams Gordon H. , Shi Yujiang , Khalil Raouf A.
Published: August 2011

Histone methylation, a determinant of chromatin structure and gene transcription, was thought to be irreversible, but recent evidence suggests that lysine-specific demethylase-1 (LSD1, Kdm1a) induces demethylation of histone H3 lysine 4 (H3K4) or H3K9 and thereby alters gene transcription. We previously demonstrated a human LSD1 phenotype associated with salt-sensitive hypertension. To test the hypothesis that LSD1 plays a role in the regulation of blood pressure (BP) via vascular mechanisms and gene transcription, we measured BP and examined vascular function and endothelial nitric oxide (NO) synthase (eNOS) expression in thoracic aorta of male wild-type (WT) and heterozygous LSD1 knockout mice (LSD1+/−) fed either a liberal salt (HS; 4% NaCl) or restricted salt diet (LS; 0.08% NaCl). BP was higher in LSD1+/−than WT mice on the HS diet but not different between LSD1+/−and WT mice on the LS diet. Further examination of the mechanisms of this salt-sensitive hypertension in LSD1+/−mice on the HS diet demonstrated that plasma renin activity and plasma levels and urinary excretion of aldosterone were less in LSD1+/−than WT, suggesting suppressed renin-angiotensin-aldosterone system. In contrast, phenylephrine (Phe)-induced aortic contraction was greater in LSD1+/−than WT mice on the HS diet. Treatment of aortic rings with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a blocker of guanylate cyclase) enhanced Phe contraction in LSD1+/−compared with WT mice on the HS diet. Acetylcholine (Ach)-induced relaxation was less in LSD1+/−than WT mice on the HS diet. Endothelium removal or pretreatment with Nω-nitro-l-arginine methyl ester (blocker of NOS) or ODQ abolished Ach-induced relaxation in aorta of WT but had minimal effect in LSD1+/−. Vascular relaxation to sodium nitroprusside, an exogenous NO donor and guanylate cyclase activator, was decreased in LSD1+/−vs. WT mice on the HS diet. RT-PCR and Western blots revealed decreased eNOS mRNA expression and eNOS and guanylate cyclase protein in the heart and aorta of LSD1+/−compared with WT mice on HS diet. Thus, during the HS diet, LSD1 deficiency is associated with hypertension, enhanced vascular contraction, and reduced relaxation via NO-cGMP pathway. The data support a role for LSD1-mediated histone demethylation in the regulation of NOS/guanylate cyclase gene expression, vascular function, and BP during the HS diet.
What do we know about mechanical strain in lung alveoli?
Authors: Roan Esra , Waters Christopher M.
Published: August 2011

The pulmonary alveolus, terminal gas-exchange unit of the lung, is composed of alveolar epithelial and endothelial cells separated by a thin basement membrane and interstitial space. These cells participate in the maintenance of a delicate system regulated not only by biological factors but also by the mechanical environment of the lung, which undergoes dynamic deformation during breathing. Clinical and animal studies as well as cell culture studies point toward a strong influence of mechanical forces on lung cells and tissues including effects on growth and repair, surfactant release, injury, and inflammation. However, despite substantial advances in our understanding of lung mechanics over the last half century, there are still many unanswered questions regarding the micromechanics of the alveolus and how it deforms during lung inflation. Therefore, the aims of this review are to draw a multidisciplinary account of the mechanics of the alveolus on the basis of its structure, biology, and chemistry and to compare estimates of alveolar deformation from previous studies.
Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis
Authors: Luciw Paul A. , Oslund Karen L. , Yang Xiao-wei , Adamson Lourdes , Ravindran Resmi , Canfield Don R. , Tarara Ross , Hirst Linda , Christensen Miles , Lerche Nicholas W. , Offenstein Heather , Lewinsohn David , Ventimiglia Frank , Brignolo Laurie , Wisner Erik R. , Hyde Dallas M.
Published: August 2011

Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines.
Homogenous protein programming in the mammalian left and right ventricle free walls
Authors: Phillips Darci , Aponte Angel M. , Covian Raul , Neufeld Edward , Yu Zu-Xi , Balaban Robert S.
Published: August 2011

Despite identical cardiac outputs, the right (RV) and left ventricle (LV) have very different embryological origins and resting workload. These differences suggest that the ventricles have different protein programming with regard to energy metabolism and contractile elements. The objective of this study was to determine the relative RV and LV protein expression levels, with an emphasis on energy metabolism. The RV and LV protein contents of the rabbit and porcine heart were determined with quantitative gel electrophoresis (2D-DIGE), mass spectrometry, and optical spectroscopy techniques. Surprisingly, the expression levels for more than 600 RV and LV proteins detected were similar. This included proteins many different compartments and metabolic pathways. In addition, no isoelectric shifts were detected in 2D-DIGE consistent with no differential posttranslational modifications in these proteins. Analysis of the RV and LV metabolic response to work revealed that the metabolic rate increases much faster with workload in the RV compared with LV. This implies that the generally lower metabolic stress of the RV actually approaches LV metabolic stress at maximum workloads. Thus, identical levels of energy conversion and mechanical elements in the RV and LV may be driven by the performance requirements at maximum workloads. In summary, the ventricles of the heart manage the differences in overall workload by modifying the amounts of cytosol, not its composition. The constant myocyte composition in the LV and RV implies that the ratio of energy metabolism and contractile elements may be optimal for the sustained cardiac contractile activity in the mammalian heart.
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

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.
Photographic Framing in the Stem Cell Debate
Authors: Dahmen Nicole S.
Published: August 2011

A growing body of research examines media framing of key scientific issues of our time, specifically, those issues that include political and moral components, such as global climate change and stem cell research. In regard to the mass media, framing refers to the process by which the media organize and make sense of the news, which has an effect on how audiences perceive that news. The majority of framing research examines textual news. Little examines the content and effects of photographic news. This study uses a pretest-posttest experimental design to test for effects of photographic framing in the stem cell research debate. In addition, the study combines a traditional framing effects study with eye-tracking data to provide for a new dimension of framing effects research. Results did not show significant effects between experimental condition and participant perception of the predominant issues in the stem cell research debate or participant perception of the message. However, on the basis of eye-tracking data, photographic framing did have a significant effect on participants’ visual attention to the given photograph. Study findings suggest that eye-tracking methodology can be an important tool to further our understanding of media effects beyond that provided by traditional methods.
Inflammation as a Marker for the Prediction of Internal Carotid Artery Restenosis Following Eversion Endarterectomy—Evidence From Clinical Studies
Authors: Tanaskovic Slobodan , Isenovic Esma R. , Radak Djordje
Published: August 2011

The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies.
Arterial Ultrasound Screening as a Tool for Coronary Risk Assessment in Asymptomatic Men and Women
Authors: Cournot Maxime , Bura Alessandra , Cambou Jean-Pierre , Taraszkiewicz Dorota , Maloizel Julie , Galinier Michel , Broutin Hélène Hanaire , Chamontin Bernard , Carrié Didier , Ferrieres Jean
Published: August 2011

One of the imaging tests most commonly used to assess cardiovascular diseases (CVDs) in daily practice is Doppler ultrasonography of the carotid and femoral arteries. We included 2709 participants with no history or symptoms of CVD; they had a risk factor assessment and a carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during a median follow-up of 6 years. Approximately, 63% of the sample presented abnormalities (carotid stenosis >50%, carotid plaque, femoral plaque, increased intima–media thickness [IMT]). A moderately increased IMT (>0.63 mm) or the presence of carotid or femoral artery plaque was related to prognosis. The associations persisted after adjustment for pretest risk, treatment with statins, and other Doppler ultrasonography abnormalities. The hazard ratio increased significantly with the number of abnormalities (varying from 2.35 [1.16-4.74] to 14.83 [6.47-33.9]).
Increased Leisure-Time Physical Activity is Associated With Lower Prevalence of the Metabolic Syndrome in 64-Year Old Women With Impaired Glucose Tolerance
Authors: Bergström Göran , Behre CarlJohan , Schmidt Caroline
Published: August 2011

The metabolic syndrome (MetS) is characterized by a cluster of factors that confer an increased risk of cardiovascular morbidity as well as mortality. It is established that physical activity (PA) has a protective role in cardiovascular morbidity and mortality, mainly through favorable effects on traditional risk factors such as body mass and blood pressure. We assessed the prevalence of MetS in a population-based sample of 64-year-old women with impaired glucose tolerance (IGT) with respect to leisure-time PA (LTPA). The results showed an inverse linear association ( P < .05) between LTPA and MetS in this group. In conclusion, this study suggests that an increased PA level has an important role in preventing MetS in women with IGT.
Body Mass Index and Hypertension Among Chinese Governmental and Institutional Employees in Beijing
Authors: Chen Tao , Li Wei , Wang Yang , Xu Tao , Hu Bo , Chen Weiwei , Zhu Manlu
Published: August 2011

Body mass index (BMI) and hypertension have been found to be associated in most studies of diverse populations; however, little information is available on whether the positive relationship is consistent among individuals at work sites. A work site-based screening was performed in 30 682 employees with a mean age of 40.3 years. In crude models, higher BMI quartiles above the lowest quartiles (BMI <20.6 kg/m2) were associated with progressively higher odds ratio (OR) of hypertension with an OR of 2.80 (95% confidence interval [CI]: 2.67-2.93) for the top quartile (BMI ≥24.6 kg/m2). Similar trends were found in fully adjusted models. Moreover, a 1-standard deviation (SD) increase in BMI was associated with a 42% significantly higher (95% CI 38-46) risk of hypertension after adjusting for other factors. Concordant relationships were revealed in all evaluated subgroups, even among those without traditional cardiovascular risk factors.
The Role of Hyperbaric Oxygen in the Treatment of Diabetic Foot Ulcers
Authors: Tiaka Elisavet K. , Papanas Nikolaos , Manolakis Anastassios C. , Maltezos Efstratios
Published: August 2011

Diabetic foot ulcers are still extremely difficult to heal. Therefore, therapeutic options to improve healing rates are continuously being explored. Hyperbaric oxygen (HBO) has been used in addition to standard treatment of the diabetic foot for more than 20 years. Evidence suggests that HBO reduces amputation rates and increases the likelihood of healing in infected diabetic foot ulcers, in association with improved tissue oxygenation, resulting in better quality of life. Nonetheless, HBO represents an expensive modality, which is only available in few centers. Moreover, adverse events necessitate a closer investigation of its safety. Finally, it is not entirely clear which patients stand to benefit from HBO and how these should be selected. In conclusion, HBO appears promising, but more experience is needed before its broad implementation in the routine care of the diabetic foot.
Child Labor and Responsible Consumers
Authors: Ballet Jérôme , Bhukuth Augendra , Carimentrand Aurélie
Published: August 2011

The basic strategy for the fight against child labor has been boycotting efforts followed by labeling practices. This article reviews the development of these practices and their impact on the hand-knotted carpet industry in India. The authors highlight the fact that though labeling has responded to many of the criticisms of boycotts, labeling too has shortcomings related to its trustworthiness in situations where information is highly asymmetrical among stakeholders. The labeling may lack credibility and, thus, arguably, has limited impact on the hand-knotted carpet industry. The article discusses why and how labeling may lack credibility. Since the article is a conceptual assessment and not an empirical study, it draws on other sources for relevant empirical information.
Rejoinder #2 to Chase-Dunn and Lawrence’s Rejoinder #2
Authors: Sanderson Stephen K
Published: August 2011

Chase-Dunn and Lawrence’s rejoinder to my rejoinder resorts to special pleading to defend WSA. They accept my argument that colonialism was not responsible for current underdevelopment in sub-Saharan Africa but contend that the slave trade was responsible. Empirical analyses show this not to be the case. They argue that Communist projects were not entirely negative because they brought peasants into the modern world. In fact, Communist projects destroyed agricultural productivity and led to the deaths of millions of peasants. They also contend that I seek to claim the moral high ground of science and objectivity. I seek no moral high ground, just a respect for facts, uncomfortable though they may be.
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.