bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Niche for Organohalide-Respiring Chloroflexi
Authors: Krzmarzick Mark J. , Crary Benjamin B. , Harding Jevon J. , Oyerinde Oyenike O. , Leri Alessandra C. , Myneni Satish C. B. , Novak Paige J.
Published: November 2011

The phylumChloroflexicontains several isolated bacteria that have been found to respire a diverse array of halogenated anthropogenic chemicals. The distribution and role of theseChloroflexiin uncontaminated terrestrial environments, where abundant natural organohalogens could function as potential electron acceptors, have not been studied. Soil samples (116 total, including 6 sectioned cores) from a range of uncontaminated sites were analyzed for the number ofDehalococcoides-likeChloroflexi16S rRNA genes present.Dehalococcoides-likeChloroflexipopulations were detected in all but 13 samples. The concentrations of organochlorine ([organochlorine]), inorganic chloride, and total organic carbon (TOC) were obtained for 67 soil core sections. The number ofDehalococcoides-likeChloroflexi16S rRNA genes positively correlated with [organochlorine]/TOC while the number ofBacteria16S rRNA genes did not.Dehalococcoides-likeChloroflexiwere also observed to increase in number with a concomitant accumulation of chloride when cultured with an enzymatically produced mixture of organochlorines. This research provides evidence that organohalide-respiringChloroflexiare widely distributed as part of uncontaminated terrestrial ecosystems, they are correlated with the fraction of TOC present as organochlorines, and they increase in abundance while dechlorinating organochlorines. These findings suggest that organohalide-respiringChlorofleximay play an integral role in the biogeochemical chlorine cycle.
Characterization, Ecological Distribution, and Population Dynamics of Saccharomyces Sensu Stricto Killer Yeasts in the Spontaneous Grape Must Fermentations of Southwestern Spain
Authors: Maqueda Matilde , Zamora Emiliano , Álvarez María L. , Ramírez Manuel
Published: November 2011

Killer yeasts secrete protein toxins that are lethal to sensitive strains of the same or related yeast species. Among the four types ofSaccharomyceskiller yeasts already described (K1, K2, K28, and Klus), we found K2 and Klus killer yeasts in spontaneous wine fermentations from southwestern Spain. Both phenotypes were encoded by medium-size double-stranded RNA (dsRNA) viruses,Saccharomyces cerevisiaevirus (ScV)-M2 and ScV-Mlus, whose genome sizes ranged from 1.3 to 1.75 kb and from 2.1 to 2.3 kb, respectively. The K2 yeasts were found in all the wine-producing subareas for all the vintages analyzed, while the Klus yeasts were found in the warmer subareas and mostly in the warmer ripening/harvest seasons. The middle-size isotypes of the M2 dsRNA were the most frequent among K2 yeasts, probably because they encoded the most intense K2 killer phenotype. However, the smallest isotype of the Mlus dsRNA was the most frequent for Klus yeasts, although it encoded the least intense Klus killer phenotype. The killer yeasts were present in most (59.5%) spontaneous fermentations. Most were K2, with Klus being the minority. The proportion of killer yeasts increased during fermentation, while the proportion of sensitive yeasts decreased. The fermentation speed, malic acid, and wine organoleptic quality decreased in those fermentations where the killer yeasts replaced at least 15% of a dominant population of sensitive yeasts, while volatile acidity and lactic acid increased, and the amount of bacteria in the tumultuous and the end fermentation stages also increased in an unusual way.
Salivaricin D, a Novel Intrinsically Trypsin-Resistant Lantibiotic from Streptococcus salivarius 5M6c Isolated from a Healthy Infant
Authors: Birri Dagim Jirata , Brede Dag Anders , Nes Ingolf F.
Published: November 2011

In this work, we purified and characterized a newly identified lantibiotic (salivaricin D) from
Streptococcus salivarius
5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (
salI
) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogens
Streptococcus pyogenes
and
Streptococcus pneumoniae
. Thus,
Streptococcus salivarius
5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium.
Enterococcus faecium of the
vanA
Genotype in Rural Drinking Water, Effluent, and the Aqueous Environment
Authors: Morris Dearbháile , Galvin Sandra , Boyle Fiona , Hickey Paul , Mulligan Martina , Cormican Martin
Published: November 2011

Total enterococci and vancomycin-resistant enterococci (VRE) were enumerated in samples of effluent (
n
= 50) and water (
n
= 167) from a number of sources. VRE were detected in the outflow of a wastewater treatment plant and in a single rural drinking water supply, suggesting potential for transmission to humans through environmental contamination.
Preliminary Safety Evaluation of a New Bacteroides xylanisolvens Isolate
Authors: Ulsemer Philippe , Toutounian Kawe , Schmidt Jens , Karsten Uwe , Goletz Steffen
Published: November 2011

Besides conferring some health benefit to the host, a bacterial strain must present an unambiguous safety status to be considered a probiotic. We here present the preliminary safety evaluation of a new
Bacteroides xylanisolvens
strain (DSM 23964) isolated from human feces. First results suggest that it may be able to provide probiotic health benefits. Its identity was confirmed by biochemical analysis, by sequencing of its 16S rRNA genes, and by DNA-DNA hybridization. Virulence determinants known to occur in the genus
Bacteroides
, such the
bft
enterotoxin and other enzymatic activities involved in the degradation of the extracellular matrix and the capsular polysaccharide PS A, were absent in this strain. The investigation of the antibiotic susceptibility indicated that strain DSM 23964 was sensitive to metronidazole, meropenem agents, and clindamycin. Resistance to penicillin and ampicillin was identified to be conferred by the β-lactamase
cepA
gene and could therefore be restored by adding β-lactamase inhibitors. The localization of the
cepA
gene in the genome of strain DSM 23964 and the absence of detectable plasmids further suggest that a transfer of β-lactamase activity or the acquisition of other antibiotic resistances are highly improbable. Taken together, the presented data indicate that the strain
B. xylanisolvens
DSM 23964 has no virulence potential. Since it also resists the action of gastric enzymes and low-pH conditions, this strain is an interesting candidate for further investigation of its safety and potential health-promoting properties.
Streptomycin-Induced Expression in Bacillus subtilis of YtnP, a Lactonase-Homologous Protein That Inhibits Development and Streptomycin Production in Streptomyces griseus
Authors: Schneider Johannes , Yepes Ana , Garcia-Betancur Juan C. , Westedt Isa , Mielich Benjamin , López Daniel
Published: November 2011

Bacillus subtilis
induces expression of the gene
ytnP
in the presence of the antimicrobial streptomycin, produced by the Gram-positive bacterium
Streptomyces griseus
.
ytnP
encodes a lactonase-homologous protein that is able to inhibit the signaling pathway required for the streptomycin production and development of aerial mycelium in
S. griseus
.
Role of IncP-1β Plasmids pWDL7::
rfp
and pNB8c in Chloroaniline Catabolism as Determined by Genomic and Functional Analyses
Authors: Król J. E. , Penrod J. T. , McCaslin H. , Rogers L. M. , Yano H. , Stancik A. D. , Dejonghe W. , Brown C. J. , Parales R. E. , Wuertz S. , Top E. M.
Published: November 2011

Broad-host-range catabolic plasmids play an important role in bacterial degradation of man-made compounds. To gain insight into the role of these plasmids in chloroaniline degradation, we determined the first complete nucleotide sequences of an IncP-1 chloroaniline degradation plasmid, pWDL7::
rfp
and its close relative pNB8c, as well as the expression pattern, function, and bioaugmentation potential of the putative 3-chloroaniline (3-CA) oxidation genes. Based on phylogenetic analysis of backbone proteins, both plasmids are members of a distinct clade within the IncP-1β subgroup. The plasmids are almost identical, but whereas pWDL7::
rfp
carries a duplicate inverted catabolic transposon, Tn
6063
, containing a putative 3-CA oxidation gene cluster,
dcaQTA1A2BR
, pNB8c contains only a single copy of the transposon. No genes for an aromatic ring cleavage pathway were detected on either plasmid, suggesting that only the upper 3-CA degradation pathway was present. The
dcaA1A2B
gene products expressed from a high-copy-number vector were shown to convert 3-CA to 4-chlorocatechol in
Escherichia coli
. Slight differences in the
dca
promoter region between the plasmids and lack of induction of transcription of the pNB8c
dca
genes by 3-CA may explain previous findings that pNB8C does not confer 3-CA transformation. Bioaugmentation of activated sludge with pWDL7::
rfp
accelerated removal of 3-CA, but only in the presence of an additional carbon source. Successful bioaugmentation requires complementation of the upper pathway genes with chlorocatechol cleavage genes in indigenous bacteria. The genome sequences of these plasmids thus help explain the molecular basis of their catabolic activities.
Mur Regulates the Gene Encoding the Manganese Transporter MntH in Brucella abortus 2308
Authors: Menscher Evan A. , Caswell Clayton C. , Anderson Eric S. , Roop R. Martin
Published: November 2011

MntH is the only high-affinity manganese transporter identified in
Brucella
. A previous study showed that MntH is required for the wild-type virulence of
Brucella abortus
2308 in mice (Anderson ES, et al., Infect. Immun.
77:
3466–3474, 2009) and indicated that the
mntH
gene is regulated in a manganese-responsive manner in this strain by a Mur homolog. In the study presented here, the transcriptional start site for
mntH
in
B. abortus
2308 was determined by primer extension analysis. Specific interactions between Mur and the
mntH
promoter region were demonstrated in an electrophoretic mobility shift assay (EMSA), and a Mur binding site was identified in the −55 to −24 region of the
mntH
promoter by DNase I footprint analysis. The specificity of the interaction of Mur with the putative Mur box was further evaluated by EMSA employing oligonucleotides in which the consensus nucleotides in this region were substituted. These studies not only confirm a direct role for Mur in the Mn-responsive regulation of
mntH
expression in
Brucella abortus
2308 but also identify the
cis
-acting elements upstream of
mntH
that are responsible for this regulation.
Sequential Closure of the Cytoplasm and Then the Periplasm during Cell Division in Escherichia coli
Authors: Skoog Karl , Söderström Bill , Widengren Jerker , von Heijne Gunnar , Daley Daniel O.
Published: November 2011

To visualize the latter stages of cell division in live
Escherichia coli
, we have carried out fluorescence recovery after photobleaching (FRAP) on 121 cells expressing cytoplasmic green fluorescent protein and periplasmic mCherry. Our data show conclusively that the cytoplasm is sealed prior to the periplasm during the division event.
The Vibrio cholerae Mannitol Transporter Is Regulated Posttranscriptionally by the MtlS Small Regulatory RNA
Authors: Mustachio Lisa Maria , Aksit Selime , Mistry Ronak H. , Scheffler Robert , Yamada Akikuni , Liu Jane M.
Published: November 2011

Vibrio cholerae
continues to pose a health threat in many developing nations and regions of the world struck by natural disasters. It is a pathogen that rapidly adapts to aquatic environments and the human small intestine. Small regulatory RNAs (sRNAs) may contribute to this adaptability. Specifically, the mannitol operon sRNA (MtlS sRNA; previously designated the IGR7 sRNA) is transcribed antisense to the 5′ untranslated region of the
mtl
operon, encoding the mannitol-specific phosphotransferase system. Mannitol is a six-carbon sugar alcohol that accumulates in the human small intestine, the primary site of
V. cholerae
colonization. To better understand the
V. cholerae
mtl
operon at a molecular level, we investigated
mtlA
expression in the presence of various carbon sources and the role of the MtlS sRNA. We observed that MtlA protein is present only in cells grown on mannitol sugar, whereas MtlS sRNA is expressed during growth on all sugars other than mannitol. In contrast,
mtlA
mRNA is expressed in similar amounts regardless of the carbon source used for bacterial growth. These observations suggest that the regulation of MtlA protein expression is a posttranscriptional event. We further demonstrate that MtlS sRNA overexpression repressed MtlA synthesis without affecting the stability of the messenger and that this process is largely independent of Hfq. We propose a model in which, when carbon sources other than mannitol are present, MtlS sRNA is transcribed, base pairs with the 5′ untranslated region of the
mtlA
mRNA, occluding the ribosome binding site, and inhibits the synthesis of the mannitol-specific phosphotransferase system.
Unveiling Unusual Features of Formation of Septal Partition and Constriction in Mycobacteria—an Ultrastructural Study
Authors: Vijay Srinivasan , Anand Deepak , Ajitkumar Parthasarathi
Published: November 2011

The ultrastructural functions of the electron-dense glycopeptidolipid-containing outermost layer (OL), the arabinogalactan-mycolic acid-containing electron-transparent layer (ETL), and the electron-dense peptidoglycan layer (PGL) of the mycobacterial cell wall in septal growth and constriction are not clear. Therefore, using transmission electron microscopy, we studied the participation of the three layers in septal growth and constriction in the fast-growing saprophytic species
Mycobacterium smegmatis
and the slow-growing pathogenic species
Mycobacterium xenopi
and
Mycobacterium tuberculosis
in order to document the processes in a comprehensive and comparative manner and to find out whether the processes are conserved across different mycobacterial species. A complete septal partition is formed first by the fresh synthesis of the septal PGL (S-PGL) and septal ETL (S-ETL) from the envelope PGL (E-PGL) in
M. smegmatis
and
M. xenopi
. The S-ETL is not continuous with the envelope ETL (E-ETL) due to the presence of the E-PGL between them. The E-PGL disappears, and the S-ETL becomes continuous with the E-ETL, when the OL begins to grow and invaginate into the S-ETL for constriction. However, in
M. tuberculosis
, the S-PGL and S-ETL grow from the E-PGL and E-ETL, respectively, without a separation between the E-ETL and S-ETL by the E-PGL, in contrast to the process in
M. smegmatis
and
M. xenopi
. Subsequent growth and invagination of the OL into the S-ETL of the septal partition initiates and completes septal constriction in
M. tuberculosis
. A model for the conserved sequential process of mycobacterial septation, in which the formation of a complete septal partition is followed by constriction, is presented. The probable physiological significance of the process is discussed. The ultrastructural features of septation and constriction in mycobacteria are unusually different from those in the well-studied organisms
Escherichia coli
and
Bacillus subtilis
.
CitA/CitB Two-Component System Regulating Citrate Fermentation in Escherichia coli and Its Relation to the DcuS/DcuR System
In Vivo
Authors: Scheu P. D. , Witan J. , Rauschmeier M. , Graf S. , Liao Y.-F. , Ebert-Jung A. , Basché T. , Erker W. , Unden G.
Published: November 2011

Citrate fermentation by
Escherichia coli
requires the function of the citrate/succinate antiporter CitT (
citT
gene) and of citrate lyase (
citCDEFXG
genes). Earlier experiments suggested that the two-component system CitA/CitB, consisting of the membrane-bound sensor kinase CitA and the response regulator CitB, stimulates the expression of the genes in the presence of citrate, similarly to CitA/CitB of
Klebsiella pneumoniae
. In this study, the expression of a chromosomal
citC-lacZ
gene fusion was shown to depend on CitA/CitB and citrate. CitA/CitB is related to the DcuS/DcuR two-component system which induces the expression of genes for fumarate respiration in response to C
4
-dicarboxylates and citrate. Unlike DcuS, CitA required none of the cognate transporters (CitT, DcuB, or DcuC) for function, and the deletion of the corresponding genes showed no effect on the expression of
citC-lacZ
. The
citAB
operon is preceded by a DcuR binding site. Phosphorylated DcuR bound specifically to the promoter region, and the deletion of
dcuS
or
dcuR
reduced the expression of
citC
. The data indicate the presence of a regulatory cascade consisting of DcuS/DcuR modulating
citAB
expression (and CitA/CitB levels) and CitA/CitB controlling the expression of the
citCDEFXGT
gene cluster in response to citrate.
In vivo
fluorescence resonance energy transfer (FRET) and the bacterial two-hybrid system (BACTH) showed interaction between the DcuS and CitA proteins. However, BACTH and expression studies demonstrated the lack of interaction and cross-regulation between CitA and DcuR or DcuS and CitB. Therefore, there is only linear phosphoryl transfer (DcuS→DcuR and CitA→CitB) without cross-regulation between DcuS/DcuR and CitA/CitB.
Patient safety in patients who occupy beds on clinically inappropriate wards: a qualitative interview study with NHS staff
Authors: Goulding Lucy , Adamson Joy , Watt Ian , Wright John
Published: November 2011

Objective

To explore NHS staff members' perceptions and experiences of the contributory factors that may underpin patient safety issues in those who are placed on a hospital ward that would not normally treat their illness (such patients are often called ‘outliers’ ‘sleep outs’ or ‘boarders’).

Design

Qualitative study using semi-structured interviews.

Setting

A single large teaching hospital in the north of England.

Participants

29 members of NHS staff (doctors, nurses and non-clinical or management staff).

Results

Five themes describing contributory factors underlying safety issues were identified: competing demands on staff time created by having patients on inappropriate wards and patients who are on the correct specialty ward to care for; poor communication between the correct specialty ward and the clinically inappropriate ward; lack of knowledge or specialist expertise on clinically inappropriate wards; an unsuitable ward environment for patients on inappropriate wards; and the characteristics of patients who are placed on clinically inappropriate wards (specifically staff perceive patients on inappropriate wards to be medically fit and therefore of lower priority and moving patients between wards may disorientate confused or impaired patients). Examples of how these contributory factors may lead to safety issues are given.

Conclusions

NHS staff report that placement of patients on clinically inappropriate wards is a specific patient safety concern. The application of James Reason's Swiss cheese model of accident causation suggests that placement on an inappropriate ward constitutes a ‘latent condition’ which may expose patients to contributory factors that underlie adverse events.
A ‘Communication and Patient Safety’ training programme for all healthcare staff: can it make a difference?
Authors: Lee Peter , Allen Kellie , Daly Michael
Published: November 2011

Communication breakdown is a factor contributing to most cases of patient harm, and this harm continues to occur at unacceptable levels. Responding to this evidence, the Metro South District of Queensland Health (Australia) has developed a communication skills training programme titled ‘Communication and Patient Safety’. The three modules, each lasting 3½ h, cover both staff-to-patient and staff-to-staff communication issues, and an unusual feature is that clinical and non-clinical staff attend together. Following positive evaluation data from our initial pilot programme (involving 350 staff in a single hospital), the programme was expanded to all five hospitals in the district, and has now been completed by over 3000 staff. The results show that despite the significant time commitment, participants find the courses useful and relevant (Kirkpatrick level 1), they learn and retain new material (level 2), and they report changes in behaviour at individual, team and facility levels (level 3). Although it remains a challenge to obtain quantitative data showing that training such as this directly improves patient safety (level 4), our qualitative and informal feedback indicates that participants and their managers perceive clear improvements in the ‘communication culture’ after a workplace team has attended the courses. Improving ‘communication for safety’ in healthcare is a worldwide imperative, and other healthcare jurisdictions should be able to obtain similar results to ours if they develop and support interactive, non-didactic training in communication skills.
Instigating change: trainee doctors' perspective: Table 1
Authors: Parvizi Nassim , Shahaney Sumera , Martin Guy , Ahmad Ahmir , Moghul Masood
Published: November 2011

In the 21st century, the core skills of trainee doctors are evolving as clinicians, leaders and innovators. Leadership skills are an essential tool for all doctors and need to be an integral part of their training and learning as set out in the General Medical Council's Good Medical Practice. It is essential to develop these skills at an early stage and continually improve them. A group of junior doctors participated in a pilot programme for leadership with the aim of executing a quality improvement (QI) project. This article describes our experiences of both the course itself and the project undertaken by our group. As part of the process of implementing change, we faced a number of challenges which contributed to our learning. These have been explored as well as potential ways to overcome them to enable the swift and smooth development of future QI projects. Using an example of a QI project looking at handover, this article demonstrates how a trainee doctor can implement their project for both professional and institutional improvement.
Myofibroblasts cause heterogeneous Cx43 reduction and are unlikely to be coupled to myocytes in the healing canine infarct
Authors: Baum Jennifer R. , Long Biao , Cabo Candido , Duffy Heather S.
Published: November 2011

Following myocardial infarction (MI) inflammatory responses transform cardiac fibroblasts to myofibroblasts, which in vitro studies show form heterocellular gap junctions with cardiac myocytes via Connexin43 (Cx43). The ability to form heterocellular junctions in the intact heart and the impact of these junctions on propagation is unclear. We used a canine model of MI and characterized the distribution and quantity of myofibroblasts in surviving epicardial cells [epicardial border zone (EBZ)]. We found a significant increase in myofibroblasts within the EBZ and no gap junction plaques between myofibroblasts and myocytes. Because myofibroblasts produce IL-1β, which downregulates Cx43, we asked whether myofibroblast proliferation causes loss of Cx43 near myofibroblast clusters. In vitro studies showed that IL-1β caused loss of Cx43 and reduced coupling. Western blot showed a significant increase of IL-1β in the EBZ, and immunohistochemistry showed a loss of Cx43 in regions of myofibroblasts in the intact heart. Additionally, dye studies in intact heart showed no coupling between myocytes and myofibroblasts. To quantify the effect of myofibroblasts on propagation we used a two-dimensional subcellular computer model of the EBZ, which showed that heterogeneities in myofibroblast density lead to conduction abnormalities. In conclusion, an increase of myofibroblasts in the infarcted heart causes heterogeneous Cx43 levels, possibly as a result of the release of IL-1β and decreased cell-cell communication, which leads to conduction abnormalities following MI.
Autophagy mechanism of right ventricular remodeling in murine model of pulmonary artery constriction
Authors: Qipshidze Natia , Tyagi Neetu , Metreveli Naira , Lominadze David , Tyagi Suresh C.
Published: November 2011

Although right ventricular failure (RVF) is the hallmark of pulmonary arterial hypertension (PAH), the mechanism of RVF is unclear. Development of PAH-induced RVF is associated with an increased reactive oxygen species (ROS) production. Increases in oxidative stress lead to generation of nitro-tyrosine residues in tissue inhibitor of metalloproteinase (TIMPs) and liberate active matrix metalloproteinase (MMPs). To test the hypothesis that an imbalance in MMP-to-TIMP ratio leads to interstitial fibrosis and RVF and whether the treatment with folic acid (FA) alleviates ROS generation, maintains MMP/TIMP balance, and regresses interstitial fibrosis, we used a mouse model of pulmonary artery constriction (PAC). After surgery mice were given FA in their drinking water (0.03 g/l) for 4 wk. Production of ROS in the right ventricle (RV) was measured using oxidative fluorescent dye. The level of MMP-2, -9, and -13 and TIMP-4, autophagy marker (p62), mitophagy marker (LC3A/B), collagen interstitial fibrosis, and ROS in the RV wall was measured. RV function was measured by Millar catheter. Treatment with FA decreased the pressure to 35 mmHg from 50 mmHg in PAC mice. Similarly, RV volume in PAC mice was increased compared with the Sham group. A robust increase of ROS was observed in RV of PAC mice, which was decreased by treatment with FA. The protein level of MMP-2, -9, and -13 was increased in RV of PAC mice in comparison with that in the sham-operated mice, whereas supplementation with FA abolished this effect and mitigated MMPs levels. The protein level of TIMP-4 was decreased in RV of PAC mice compared with the Sham group. Treatment with FA helped PAC mice to improve the level of TIMP-4. To further support the claim of mitophagy occurrence during RVF, the levels of LC3A/B and p62 were measured by Western blot and immunohistochemistry. LC3A/B was increased in RV of PAC mice. Similarly, increased p62 protein level was observed in RV of PAC mice. Treatment with FA abolished this effect in PAC mice. These results suggest that FA treatment improves MMP/TIMP balance and ameliorates mitochondrial dysfunction that results in protection of RV failure during pulmonary hypertension.
Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance
Authors: Poole David C. , Hirai Daniel M. , Copp Steven W. , Musch Timothy I.
Published: November 2011

The defining characteristic of chronic heart failure (CHF) is an exercise intolerance that is inextricably linked to structural and functional aberrations in the O2 transport pathway. CHF reduces muscle O2 supply while simultaneously increasing O2 demands. CHF severity varies from moderate to severe and is assessed commonly in terms of the maximum O2 uptake, which relates closely to patient morbidity and mortality in CHF and forms the basis for Weber and colleagues' ( 167 ) classifications of heart failure, speed of the O2 uptake kinetics following exercise onset and during recovery, and the capacity to perform submaximal exercise. As the heart fails, cardiovascular regulation shifts from controlling cardiac output as a means for supplying the oxidative energetic needs of exercising skeletal muscle and other organs to preventing catastrophic swings in blood pressure. This shift is mediated by a complex array of events that include altered reflex and humoral control of the circulation, required to prevent the skeletal muscle “sleeping giant” from outstripping the pathologically limited cardiac output and secondarily impacts lung (and respiratory muscle), vascular, and locomotory muscle function. Recently, interest has also focused on the dysregulation of inflammatory mediators including tumor necrosis factor-α and interleukin-1β as well as reactive oxygen species as mediators of systemic and muscle dysfunction. This brief review focuses on skeletal muscle to address the mechanistic bases for the reduced maximum O2 uptake, slowed O2 uptake kinetics, and exercise intolerance in CHF. Experimental evidence in humans and animal models of CHF unveils the microvascular cause(s) and consequences of the O2 supply (decreased)/O2 demand (increased) imbalance emblematic of CHF. Therapeutic strategies to improve muscle microvascular and oxidative function (e.g., exercise training and anti-inflammatory, antioxidant strategies, in particular) and hence patient exercise tolerance and quality of life are presented within their appropriate context of the O2 transport pathway.
Dendritic cell functional properties in a three-dimensional tissue model of human lung mucosa
Authors: Hoang Anh Thu Nguyen , Chen Puran , Juarez Julius , Sachamitr Patty , Billing Bo , Bosnjak Lidija , Dahlén Barbro , Coles Mark , Svensson Mattias
Published: November 2011

In lung tissue, dendritic cells (DC) are found in close association with the epithelial cell layer, and there is evidence of DC regulation by the epithelium; that epithelial dysfunction leads to overzealous immune cell activation. However, dissecting basic mechanisms of DC interactions with epithelial cells in human tissue is difficult. Here, we describe a method to generate a three-dimensional organotypic model of the human airway mucosa in which we have implanted human DC. The model recapitulates key anatomical and functional features of lung mucosal tissue, including a stratified epithelial cell layer, deposition of extracellular matrix proteins, and the production of tight junction and adherence junction proteins. Labeling of fixed tissue model sections and imaging of live tissue models also revealed that DC distribute in close association with the epithelial layer. As functional properties of DC may be affected by the local tissue microenvironment, this system provides a tool to study human DC function associated with lung mucosal tissue. As an example, we report that the lung tissue model regulates the capacity of DC to produce the chemokines CCL17, CCL18, and CCL22, leading to enhanced CCL18 expression and reduced CCL17 and CCL22 expression. This novel tissue model thus provides a tool well suited for a wide range of studies, including those on the regulation of DC functional properties within the local tissue microenvironment during homeostasis and inflammatory reactions.
Tribological Effects of Mineral-Oil Lubricant Contamination with Biofuels: A Pin-on-Disk Tribometry and Wear Study
Authors: Shanta S. M. , Molina G. J. , Soloiu V.
Published: November 2011

Use of biodiesel produces engine oil dilution because of unburned biodiesel impinging on cold walls of the combustion chamber, being scrapped to the oil pan, and leading to changes of oil friction, wear and lubricity properties. In this paper, mixtures of SAE 15W-40 oil, which were contaminated by known percentages of the biodiesels from canola oil, peanut oil, soybean oil, and chicken fat, were tested in a pin-on-disk tribometer. A contact was employed of AISI 1018 steel disk and AISI 316 stainless-steel ball for pin material, and friction force and specific wear were measured. Wear on the disk surfaces showed that any degree of mineral-oil dilution by the tested biodiesels reduces the wear protection of engine oil even at small mixture percentages. However, these reductions were not substantially different than those observed for same percentages of dilution of mineral oil by fossil diesel. The tested mixture of oil contaminated with animal fat feedstock (e.g., chicken fat) biodiesel showed the best wear behavior as compared to those for the other tested mixtures (of mineral oil with vegetable feedstock biodiesel dilutions). Obtained results are discussed as baseline for further studies in a renewable energy multidisciplinary approach on biofuels and biolubes.
Extended Extragradient Methods for Generalized Variational Inequalities
Authors: Yao Yonghong , Liou Yeong-Cheng , Li Cun-Lin , Lin Hui-To
Published: November 2011

We suggest a modified extragradient method for solving the generalized variational inequalities in a Banach space. We prove some strong convergence results under some mild conditions on parameters. Some special cases are also discussed.
Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration
Authors: Zampros Ilias , Praidou Anna , Brazitikos Periklis , Ekonomidis Panagiotis , Androudi Sofia
Published: November 2011

Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes.
Fibromyalgia and Depression
Authors: Gracely Richard H. , Ceko Marta , Bushnell M. Catherine
Published: November 2011

Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromyalgia and depression and include laboratory findings on the role of depression in fibromyalgia. Further, we comment on several aspects of fibromyalgia which support the development of reactive depression, substantially more so than in other chronic pain syndromes. However, while sharing many features with depression, fibromyalgia is associated with somatic comorbidities and absolutely defined by fluctuating spontaneous widespread pain. Fibromyalgia may, therefore, be more appropriately grouped together with other functional pain disorders, while psychologically distressed subgroups grouped additionally or solely with affective spectrum disorders.
Stress-Regulated Transcription Factor ATF4 Promotes Neoplastic Transformation by Suppressing Expression of the INK4a/ARF Cell Senescence Factors
Authors: Horiguchi Michiko , Koyanagi Satoru , Okamoto Akinori , Suzuki Satoshi O. , Matsunaga Naoya , Ohdo Shigehiro
Published: November 2011

Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored. Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes. Strikingly, primary embryo fibroblasts from ATF4-deficient mice were resistant to transformation by coexpression of H-rasV12 and SV40 large T antigen. In wild-type cells these oncogenes induced expression of the murine Atf4 gene along with the cyclin-dependent kinase inhibitor Cdkn2a, which encodes the cell senescence-associated proteins p16INK4 and p19ARF. Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation. Conversely, genetic ablation of ATF4 led to constitutive expression of p16INK4a and p19ARF, triggering cellular senescence. Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence. Cancer Res; 72(2); 395–401. ©2011 AACR.
A Large Candidate Gene Survey Identifies the
KCNE1
D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes
Authors: Kääb Stefan , Crawford Dana C. , Sinner Moritz F. , Behr Elijah R. , Kannankeril Prince J. , Wilde Arthur A.M. , Bezzina Connie R. , Schulze-Bahr Eric , Guicheney Pascale , Bishopric Nanette H. , Myerburg Robert J. , Schott Jean-Jacques , Pfeufer Arne , Beckmann Britt-Maria , Martens Eimo , Zhang Taifang , Stallmeyer Birgit , Zumhagen Sven , Denjoy Isabelle , Bardai Abdennasser , Van Gelder Isabelle C. , Jamshidi Yalda , Dalageorgou Chrysoula , Marshall Vanessa , Jeffery Steve , Shakir Saad , Camm A. John , Steinbeck Gerhard , Perz Siegfried , Lichtner Peter , Meitinger Thomas , Peters Annette , Wichmann H.-Erich , Ingram Christiana , Bradford Yuki , Carter Shannon , Norris Kris , Ritchie Marylyn D. , George Alfred L. , Roden Dan M.
Published: November 2011

Background—

Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS.

Methods and Results—

In a case-control setting, we included 176 patients of European descent from North America and Europe with diLQTS, defined as documented torsades de pointes during treatment with a QT-prolonging drug. Control samples were obtained from 207 patients of European ancestry who displayed <50 ms QT lengthening during initiation of therapy with a QT-prolonging drug and 837 control subjects from the population-based KORA study. Subjects were successfully genotyped at 1424 single-nucleotide polymorphisms (SNPs) in 18 candidate genes including 1386 SNPs tagging common haplotype blocks and 38 nonsynonymous ion channel gene SNPs. For validation, we used a set of cases (n=57) and population-based control subjects of European descent. The SNP
KCNE1
D85N (rs1805128), known to modulate an important potassium current in the heart, predicted diLQTS with an odds ratio of 9.0 (95% confidence interval, 3.5–22.9). The variant allele was present in 8.6% of cases, 2.9% of drug-exposed control subjects, and 1.8% of population control subjects. In the validation cohort, the variant allele was present in 3.5% of cases and in 1.4% of control subjects.

Conclusions—

This high-density candidate SNP approach identified a key potassium channel susceptibility allele that may be associated with the rare adverse drug reaction torsades de pointes.
Burden of informal care giving to patients with psychoses: A descriptive and methodological study
Authors: Flyckt Lena , Löthman Anna , Jörgensen Leif , Rylander Anders , Koernig Thomas
Published: November 2011

Background:

There is a lack of studies of the size of burden associated with informal care giving in psychosis.

Aims:

To evaluate the objective and subjective burden of informal care giving to patients with psychoses, and to compare a diary and recall method for assessments of objective burden.

Method:

Patients and their informal caregivers were recruited from nine Swedish psychiatric outpatient centres. Subjective burden was assessed at inclusion using the CarerQoL and COPE index scales. The objective burden (time and money spent) was assessed by the caregivers daily using diaries over four weeks and by recall at the end of weeks 1 and 2.

Results:

One-hundred and seven patients (53% females; mean age 43 ± 11) and 118 informal caregivers (67%; 58 ± 15 years) were recruited. Informal caregivers spent 22.5 hours/week and about 14% of their gross income on care-related activities. The time spent was underestimated by two to 20 hours when assessed by recall than by daily diary records. The most prominent aspects of the subjective burden were mental problems.

Conclusion:

Despite a substantial amount of time and money spent on care giving, the informal caregivers perceived the mental aspects of burden as the most troublesome. The informal caregiver burden is considerable and should be taken into account when evaluating effects of health care provided to patients with psychoses.
Sources of parental burden in a UK sample of first-generation North Indian Punjabi Sikhs and their white British counterparts
Authors: Lloyd Helen , Singh Pratima , Merritt Rowena , Shetty Adarsh , Singh Swaran , Burns Tom
Published: November 2011

Objective:

The correlates of parental burden in schizophrenia may differ between ethnic groups, but few studies have examined this in a UK setting. Our aim was to identify the correlates of burden in a UK sample of first-generation North Indian Punjabi Sikh parents and their white British counterparts.

Method:

Test the association of burden with a series of clinical, social and service use variables and control for potential confounding factors in a model predicting drivers of burden in a combined sample of the above.

Results:

The strongest correlates of burden were patient symptoms and parental distress. Differences in correlates of burden between the groups emerged when individual components of service use and parental social network were tested. The group comparisons also revealed differences in expressed emotion (EE) and social networks.

Conclusion:

The similarities in sources of burden between the groups could be explained by a commonality of sociocultural and economic experience, resulting from the successful acculturation and affluence of this British Sikh group. The differences between the groups may be related to enduring cultural factors such as kin support, since larger family groups were associated with low burden in the British Sikh group. The nature of EE in this British Sikh group may explain why it was not associated with burden in this sample.
Associations Between Filial Responsibility and Caregiver Well-Being
Authors: Funk Laura M. , Chappell Neena L. , Liu Guiping
Published: November 2011

A sense of filial responsibility, particularly where it is a strong cultural norm, may be beneficial for caregiver self-rated health and well-being. The purpose of this study was to examine associations between filial responsibility attitudes and both self-rated health and well-being within three cultural groups: Caucasian Canadian ( n = 100), Chinese Canadian ( n = 90), and Hong Kong Chinese ( n = 125). Respondents were interviewed in person using a structured questionnaire. Multivariate analyses for the entire sample indicated associations between filial responsibility attitudes and both self-rated health status and overall well-being. Analyses performed within each cultural subgroup indicated that filial responsibility is associated with worse self-rated health in the Caucasian Canadian group. The results suggest caution in assuming that filial responsibility attitudes will be beneficial for caregiver outcomes; there may also be cultural variation.
The Relationship of Job and Elder Caregiving Involvement to Work-Caregiving Conflict and Work Costs
Authors: Gordon Judith R. , Rouse Elizabeth D.
Published: November 2011

This article examines the relationship between job and elder caregiving involvement, bi-directional work-caregiving conflict (work interfering with caregiving [WIC] and caregiving interfering with work [CIW]), and work costs (job interruptions and job changes). Specifically, we consider the effects of both behavioral and psychological involvement and external and internal work caregiving conflict in a sample of 583 women between the ages of 50 and 64 who work full-time and have significant elder caregiving responsibilities. A telephone survey was administered using random-digit-dial procedures. Structural equation model analyses confirmed that behavioral job involvement was associated with external CIW, psychological job involvement was associated with internal WIC and internal CIW, behavioral caregiving involvement was associated with external CIW and work costs, and psychological caregiving involvement was associated with internal CIW. Internal WIC, external CIW, and internal CIW were associated with job costs. Some mediation, particularly through external and internal CIW, occurred.
Practical and Analytic Issues in the Electronic Assessment of Adherence
Authors: Cook Paul , Schmiege Sarah , McClean Margaret , Aagaard Laurra , Kahook Malik
Published: November 2011

Although medication adherence can be measured many ways, researchers often view electronic dose monitoring devices like the Medication Event Monitoring Systems (MEMS) as more valid than patient self-reports. MEMS are popular but have potential problems. Based on the literature and MEMS data analyses, the authors suggest the following approaches: (a) a 1- to 2-month run-in should be used to reduce MEMS reactivity, (b) MEMS should be used with other measures of adherence, (c) adherence should be measured continuously, or a cutoff should be defined based on pharmacological properties of the medication and the consequences of nonadherence, (d) MEMS data usually should be aggregated weekly or monthly and evaluated using multilevel modeling, (e) MEMS-based screening for nonadherence may miss some patients in need of intervention, and (f) researchers should use strategies like training patients to use MEMS and purchasing extra MEMS caps to improve the completeness and accuracy of MEMS data.
Cosmopolitanism in a global perspective: An international comparison of open-minded orientations and identity in relation to globalization
Authors: Pichler Florian
Published: November 2011

Cosmopolitanism increasingly features as a reference to describe contemporary structures of a globalized world. This article adds a critical examination of micro-level dimensions of such cosmopolitanism vigilant to the ideas about specific attitudes and global community. Who shares cosmopolitan orientations or sees oneself as world citizen? Are country differences attributable to globalization? Using data from the World Values Surveys 2005–8, cross-national comparative analyses suggest that various manifestations of cosmopolitanism – ethics, politics and identity – relate differently to socioeconomic characteristics and degrees of globalization. The study provides evidence that cosmopolitan orientations are more often found in the globalized world but, surprisingly, global identity is more widespread in other parts of the world. Implications of these findings are discussed.
Canadian development workers, transnational encounters and cultures of cosmopolitanism
Authors: Cook Nancy
Published: November 2011

This article focuses on cosmopolitanism as an object of sociological analysis, through an empirical study of Canadian development workers who were posted in Pakistan for extended periods of time and have subsequently resumed their lives in Canada. These global migrants developed various attachments to Pakistani culture and people through their transnational experiences. Employing a continuum of cosmopolitanism, the article describes these attachments, which, it argues, form the basis of a tentative and ambivalent culture of cosmopolitanism as it is lived by these development workers on their return to Canada. The study’s aim is to clarify the concept of cosmopolitanism by documenting the emergence of a new sociality characterized by global connectivities that engender justice-oriented alliances and solidarities.