bluuebunny/crossref_metadata_2025 huggingface dataset:
Further evidence on relative and incremental information content of EVA and traditional performance measures from select Indian companies
Authors: Kumar Satish , Sharma A.K.
Published: November 2011

Purpose

The main objective of this study is to examine the claim of economic value added (EVA) proponents about its superiority as a financial performance measure compared to five traditional performance measures, i.e. net operating profit after tax (NOPAT), cash flow from operations (OCF), earnings per share (EPS), return on capital employed (ROCE) and return on equity (ROE) in Indian manufacturing sector, and simultaneously provide its empirical evidences. To achieve this, relative and incremental information content of various performance measures and their relationship with market value added (MVA) is tested and examined.

Design/methodology/approach

Principal component analysis (PCA) is one of the important multivariate methods utilized in business research for data reduction, latent variable modeling, multicollinearity resolution, etc. The present sample consists of 608 firm‐year observations from the Indian manufacturing sector for the period 2000‐2007. Firstly, principal component analysis (PCA) is employed to determine the important variables that explain market value. Secondly, alongside PCA, multiple regression models (OLS) are used to examine the relative and incremental information content of EVA and traditional performance measures.

Findings

These results about PCA reveal that variables like NOPAT, OCF, ROE, ROCE and EVA have maximum influence on the market value (MVA) of the sample companies, whereas EPS has a negative loading, so, EPS is discarded for further analysis. Further, the PCA loading matrix reveals that NOPAT, OCF, ROE and ROCE outscore EVA. The regression results regarding the relative information content test reveal that NOAPT and OCF outperform EVA in explaining the market value of Indian companies. The incremental information content test shows that EVA makes a marginal contribution to information content beyond NOPAT, OCF, ROCE and ROE. Overall, these empirical results about Indian companies do not support the Stern Stewart hypothesis that EVA is superior to traditional accounting‐based measures in association with market value of the firm.

Originality/value

The study concludes that along with financial variables, other non‐financial variables such as employees, product quality, etc., should be considered in order to capture the unexplained variation in the market value of Indian companies.
The effect of the board structure on earnings management: evidence from Portugal
Authors: Geraldes Alves Sandra Maria
Published: November 2011

Purpose

This study aims to extend previous research by examining empirically how board structure affects the magnitude of earnings management for companies listed in Portugal. In particular, the paper focuses on the main characteristics of the board structure that are highlighted by the Portuguese Securities Market Supervisory Authority recommendations, i.e. board size, board composition and board's monitoring committees.

Design/methodology/approach

The OLS regression model is used to examine the effect of the board structure on earnings management for a sample of 34 non‐financial listed Portuguese companies for the years 2002 to 2007.

Findings

The results support the predicted non‐linear relationship between board size and earnings management. It is also found that discretionary accruals are negatively related to board composition. However, no evidence is found that the existence of an audit committee affects the levels of earnings management.

Practical implications

The findings based on this study provide useful information for regulators in other countries. The results also provide useful information for investors in evaluating the impact of board structure on earnings quality, especially under concentrated ownership.

Originality/value

The major contribution of the current study is that, in contrast to similar studies, it does not assume that the two views on how board size associates with firms' earnings management behaviour are mutually exclusive. In addition, this paper is the first empirical study to investigate the effect of the board structure on earnings management in Portugal.
Attention deficit hyperactivity disorder: a lifespan genetic perspective
Authors: Merwood Andrew , Asherson Philip
Published: November 2011

Purpose

– Attention deficit hyperactivity disorder (ADHD) is a common disorder that is highly prevalent in children and frequently persists into adulthood. The purpose of this paper is to consider the need for practitioners to be aware of the disorder.

Design/methodology/approach

– This paper reviews quantitative genetic findings in ADHD, primarily focussing on twin studies that describe the role of genetic influences throughout the lifespan and the associated overlap between ADHD and other syndromes, disorders and traits.

Findings

– This paper concludes that ADHD is a lifespan condition that shares genetic risk factors with other psychiatric, neurodevelopmental disorders and intellectual disabilities.

Originality/value

– This paper makes the case that clinicians working in the area of intellectual disability should be fully aware of the potential impact of ADHD and its associated impairments.
Guidelines for the diagnosis and management of hereditary spherocytosis – 2011 update
Authors: Bolton‐Maggs Paula H. B. , Langer Jacob C. , Iolascon Achille , Tittensor Paul , King May‐Jean
Published: November 2011

Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton‐Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin‐5‐maleimide (EMA) binding test has been validated in a number of studies with understanding of its limitations.
Some (worms) like it hot: fish parasites grow faster in warmer water, and alter host thermal preferences
Authors: Macnab Vicki , Barber Iain
Published: November 2011

Elevated environmental temperatures associated with anthropogenic warming have the potential to impact host‐parasite interactions, with consequences for population health and ecosystem functioning. One way that elevated temperatures might influence parasite prevalence and intensity is by increasing life cycle completion rates. Here, we investigate how elevated temperatures impact a critical phase of the life cycle of the bird tapewormSchistocephalus solidus– the growth of plerocercoid larvae in host fish (three‐spined sticklebacksGasterosteus aculeatus). By 8 weeks post‐infection, plerocercoids recovered from experimentally infected sticklebacks held at 20 °C weighed on average 104.9 mg, with all exceeding 50 mg, the mass considered consistently infective to definitive hosts. In contrast, plerocercoids from sticklebacks held at 15 °C weighed on average 26.5 mg, with none exceeding 50 mg. As small increases in plerocercoid mass affect adult fecundity disproportionately in this species, enhanced plerocercoid growth at higher temperatures predicts dramatically increased output of infective parasite stages. Subsequent screening of thermal preferences of sticklebacks from a population with endemicS. solidusinfection demonstrated that fish harbouring infective plerocercoids show significant preferences for warmer temperatures. Our results therefore indicate that parasite transmission might be affected in at least two ways under anthropogenic warming; by enhancing rates of parasite growth and development, and by increasing the likelihood of hosts being able to seek out proliferating warmer microhabitats. Furthermore, our results suggest the potential for positive feedback between parasite growth and host thermal preferences, which could dramatically increase the effects of even small temperature increases. We discuss the possible mechanisms underpinning our results, their likely ecological consequences and highlight key areas for further research.
The 2011 Nobel Prize in Physiology or Medicine
Authors: Volchenkov Roman , Sprater Florian , Vogelsang Petra , Appel Silke
Published: November 2011

The 2011 Noble Prize in Physiology or Medicine was awarded to Bruce A. Beutler, Jules A. Hoffmann and Ralph M. Steinman for their groundbreaking research within immunology. Bruce A. Beutler and Jules A. Hoffmann were recognized for their discoveries on Toll and Toll‐like receptor activation of innate immunity in fruit fly and mammals, respectively. Ralph M. Steinman received the award for the discovery of dendritic cells, a cell type bridging innate and adaptive immunity, and how these cells orchestrate immune responses.
Cross‐reactions vs co‐sensitization evaluated by in silico motifs and in vitro IgE microarray testing
Authors: Pfiffner P. , Stadler B. M. , Rasi C. , Scala E. , Mari A.
Published: November 2011

To cite this article: Pfiffner P, Stadler BM, Rasi C, Scala E, Mari A. Cross‐reactions vs co‐sensitization evaluated by in silico motifs and in vitro IgE microarray testing. Allergy 2012; 67: 210–216.

Background and objective:  Using an in silico allergen clustering method, we have recently shown that allergen extracts are highly cross‐reactive. Here we used serological data from a multi‐array IgE test based on recombinant or highly purified natural allergens to evaluate whether co‐reactions are true cross‐reactions or co‐sensitizations by allergens with the same motifs.

Methods:  The serum database consisted of 3142 samples, each tested against 103 highly purified natural or recombinant allergens. Cross‐reactivity was predicted by an iterative motif‐finding algorithm through sequence motifs identified in 2708 known allergens.

Results:  Allergen proteins containing the same motifs cross‐reacted as predicted. However, proteins with identical motifs revealed a hierarchy in the degree of cross‐reaction: The more frequent an allergen was positive in the allergic population, the less frequently it was cross‐reacting and vice versa. Co‐sensitization was analyzed by splitting the dataset into patient groups that were most likely sensitized through geographical occurrence of allergens. Interestingly, most co‐reactions are cross‐reactions but not co‐sensitizations.

Conclusions:  The observed hierarchy of cross‐reactivity may play an important role for the future management of allergic diseases.
Long‐term results of stapled haemorrhoidopexy in a prospective single centre study of 153 patients with 1–6 years’ follow‐up
Authors: Gerjy R. , Derwinger K. , Lindhoff‐Larson A. , Nyström P.‐O.
Published: November 2011

Aim  The long‐term results of stapled haemorrhoidopexy for prolapsed haemorrhoids were assessed using uniform methods to acquire data and pre‐set definitions of failure, recurrence, residual symptoms and impaired continence.

Method  From October 1999 to May 2005, 153 patients underwent a stapled haemorrhoidopexy and were enrolled prospectively. They were assessed preoperatively, postoperatively and at the end of the study from replies to a questionnaire about symptoms and continence. Preoperatively, manual reduction of prolapse was required in 103 patients, skin tags were found in 115 patients (circumferential in 22) and impaired continence in 63.

Results  In all, 145 patients completed preoperative and long‐term protocols and were analysed as paired data, at a mean follow‐up of 32 months. Failure to control the prolapse or recurrence was seen in 19 (13%) patients including nine reoperations for prolapse. Symptoms improved from 8.1 to 2.5 points on a 15‐point scale (P = 0.001). Symptoms were not controlled in 25 (17%) patients. Continence improved from 4.7 to 2.9 points on a 15‐point scale (P = 0.001). Twenty‐five (17%) patients still had a continence disturbance. Altogether 51 (35%) patients had a deficient outcome with respect to prolapse, symptoms or continence. There were no major adverse events.

Conclusion  Restoration of the anal anatomy by stapled haemorrhoidopexy resulted in a significant improvement in haemorrhoid‐associated symptoms and continence but a third of patients had poor symptom control including 13% with persisting prolapse.
A 5‐year prospective study of predictors for disability pension among patients with major depressive disorder
Authors: Holma I. A. K. , Holma K. M. , Melartin T. K. , Rytsälä H. J. , Isometsä E. T.
Published: November 2011

Holma IAK, Holma KM, Melartin TK, Rytsälä HJ, Isometsä ET. A 5‐year prospective study of predictors for disability pension among patients with major depressive disorder.

Objective:  There is a scarcity of prospective long‐term studies on work disability caused by depression. We investigated predictors for disability pension among psychiatric patients with MDD.

Method:  The Vantaa Depression Study followed up prospectively 269 psychiatric in‐ and out‐patients with DSM‐IV MDD for 5 years with a life chart, including 230 (91.3%) patients belonging to labour force. Information on disability pensions was obtained from interviews, patient records and registers.

Results:  Within 5 years, 20% of the patients belonging to labour force at baseline were granted a disability pension. In multivariate analyses, the significant baseline predictors for granted disability pension were age ≥50 years (HR = 3.91, P < 0.001), subjective inability to work (HR = 2.14, P = 0.008) and introversion (HR = 1.08, P = 0.049). When follow‐up variables were included, the predictors were age more than 50 (OR = 6.25, P < 0.001), proportion of time spent depressed (OR = 14.6, P < 0.001), number of comorbid somatic disorders (OR = 1.47, P = 0.013) and lack of vocational education (OR = 2.38, P = 0.032).

Conclusion:  Of psychiatric patients with depression, one‐fifth were granted a disability pension within 5 years. Future disability pension can be predicted by baseline older age, personality factors, functional disability, lack of vocational education and comorbid somatic disorders. Longitudinally, accumulation of time spent depressed appears decisive for pensioning.
Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification
Authors: Lackner Michaela , Najafzadeh Mohammad Javad , Sun Jiufeng , Lu Qiaoyun , de Hoog G. Sybren
Published: November 2011

ThePseudallescheria boydiicomplex, comprising environmental pathogens withScedosporiumanamorphs, has recently been subdivided into five main species:Scedosporium dehoogii,S. aurantiacum,Pseudallescheria minutispora,P. apiosperma, andP. boydii, while the validity of some other taxa is being debated. SeveralPseudallescheriaandScedosporiumspecies are indicator organisms of pollution in soil and water.Scedosporium dehoogiiin particular is enriched in soils contaminated by aliphatic hydrocarbons. In addition, the fungi may cause life-threatening infections involving the central nervous system in severely impaired patients. For screening purposes, rapid and economic tools for species recognition are needed. Our aim is to establish rolling circle amplification (RCA) as a screening tool for species-specific identification ofPseudallescheriaandScedosporium. With this aim, a set of padlock probes was designed on the basis of the internal transcribed spacer (ITS) region, differing by up to 13 fixed mutations. Padlock probes were unique as judged from sequence comparison by BLAST search in GenBank and in dedicated research databases at CBS (Centraalbureau voor Schimmelcultures Fungal Biodiversity Centre). RCA was applied as anin vitrotool, tested with pure DNA amplified from cultures. The species-specific padlock probes designed in this study yielded 100% specificity. The method presented here was found to be an attractive alternative to identification by restriction fragment length polymorphism (RFLP) or sequencing. The rapidity (<1 day), specificity, and low costs make RCA a promising screening tool for environmentally and clinically relevant fungi.
Culture and Molecular Method for Detection of Mycobacterium tuberculosis Complex and Mycobacterium avium subsp. paratuberculosis in Milk and Dairy Products
Authors: Messelhäusser U. , Kämpf P. , Hörmansdorfer S. , Wagner B. , Schalch B. , Busch U. , Höller C. , Wallner P. , Barth G. , Rampp A.
Published: November 2011

A combined molecular and cultural method for the detection of the
Mycobacterium tuberculosis
complex (MTBC) and
Mycobacterium avium
subsp.
paratuberculosis
was developed and tested with artificially contaminated milk and dairy products. Results indicate that the method can be used for a reliable detection as a basis for first risk assessments.
Association of Constitutive Hyperphosphorylation of Hsf1p with a Defective Ethanol Stress Response in Saccharomyces cerevisiae Sake Yeast Strains
Authors: Noguchi Chiemi , Watanabe Daisuke , Zhou Yan , Akao Takeshi , Shimoi Hitoshi
Published: November 2011

Modern sake yeast strains, which produce high concentrations of ethanol, are unexpectedly sensitive to environmental stress during sake brewing. To reveal the underlying mechanism, we investigated a well-characterized yeast stress response mediated by a heat shock element (HSE) and heat shock transcription factor Hsf1p in
Saccharomyces cerevisiae
sake yeast. The HSE-
lacZ
activity of sake yeast during sake fermentation and under acute ethanol stress was severely impaired compared to that of laboratory yeast. Moreover, the Hsf1p of modern sake yeast was highly and constitutively hyperphosphorylated, irrespective of the extracellular stress. Since
HSF1
allele replacement did not significantly affect the HSE-mediated ethanol stress response or Hsf1p phosphorylation patterns in either sake or laboratory yeast, the regulatory machinery of Hsf1p is presumed to function differently between these types of yeast. To identify phosphatases whose loss affected the control of Hsf1p, we screened a series of phosphatase gene deletion mutants in a laboratory strain background. Among the 29 mutants, a Δ
ppt1
mutant exhibited constitutive hyperphosphorylation of Hsf1p, similarly to the modern sake yeast strains, which lack the entire
PPT1
gene locus. We confirmed that the expression of laboratory yeast-derived functional
PPT1
recovered the HSE-mediated stress response of sake yeast. In addition, deletion of
PPT1
in laboratory yeast resulted in enhanced fermentation ability. Taken together, these data demonstrate that hyperphosphorylation of Hsf1p caused by loss of the
PPT1
gene at least partly accounts for the defective stress response and high ethanol productivity of modern sake yeast strains.
Locked Nucleic Acid and Flow Cytometry-Fluorescence
In Situ
Hybridization for the Detection of Bacterial Small Noncoding RNAs
Authors: Robertson Kelly L. , Vora Gary J.
Published: November 2011

We describe the development and testing of a high-throughput method that enables the detection of small noncoding RNAs (ncRNAs) from single bacterial cells using locked nucleic acid probes (LNA) and flow cytometry-fluorescence
in situ
hybridization (flow-FISH). The LNA flow-FISH method and quantitative reverse transcription-PCR (qRT-PCR) were used to monitor the expression of three ncRNAs (6S, CsrB, and TPP-2) in
Vibrio campbellii
ATCC BAA-1116 cultures during lag phase, mid-log phase, and stationary phase. Both LNA flow-FISH and qRT-PCR revealed that CsrB and TPP-2 were highly expressed during lag phase but markedly reduced in mid-log phase and stationary phase, whereas 6S demonstrated no to little expression during lag phase but increased thereafter. Importantly, while LNA flow-FISH and qRT-PCR demonstrated similar overall expression trends, only LNA flow-FISH, which enabled the detection of ncRNAs in individual cells as opposed to the lysate-based ensemble measurements generated by qRT-PCR, was able to capture the cell-to-cell heterogeneity in ncRNA expression. As such, this study demonstrates a new method that simultaneously enables the
in situ
detection of ncRNAs and the determination of gene expression heterogeneity within an isogenic bacterial population.
Disease Dynamics and Persistence of Musca domestica Salivary Gland Hypertrophy Virus Infections in Laboratory House Fly (Musca domestica) Populations
Authors: Lietze Verena-Ulrike , Geden Christopher J. , Doyle Melissa A. , Boucias Drion G.
Published: November 2011

Past surveys of feral house fly populations have shown that
Musca domestica
salivary gland hypertrophy virus (MdSGHV) has a worldwide distribution, with an average prevalence varying between 0.5% and 10%. How this adult-specific virus persists in nature is unknown. In the present study, experiments were conducted to examine short-term transmission efficiency and long-term persistence of symptomatic MdSGHV infections in confined house fly populations. Average rates of disease transmission from virus-infected to healthy flies in small populations of 50 or 100 flies ranged from 3% to 24% and did not vary between three tested geographical strains that originated from different continents. Introduction of an initial proportion of 40% infected flies into fly populations did not result in epizootics. Instead, long-term observations demonstrated that MdSGHV infection levels declined over time, resulting in a 10% infection rate after passing through 10 filial generations. In all experiments, induced disease rates were significantly higher in male flies than in female flies and might be explained by male-specific behaviors that increased contact with viremic flies and/or virus-contaminated surfaces.
Characterization of Streptomyces padanus JAU4234, a Producer of Actinomycin X
2
, Fungichromin, and a New Polyene Macrolide Antibiotic
Authors: Xiong Zhi-Qiang , Zhang Zhi-Ping , Li Jiang-Huai , Wei Sai-Jin , Tu Guo-Quan
Published: November 2011

Strain JAU4234, identified as
Streptomyces padanus
, was isolated from soil collected in Jiangxi Province, China. It produced actinomycin X2, fungichromin, and a new polyene macrolide compound with antifungal activity, antifungalmycin 702. Antifungalmycin 702 had good general antifungal activity and may have potential future agricultural and/or clinical applications.
A Trypanosomal Pentatricopeptide Repeat Protein Stabilizes the Mitochondrial mRNAs of Cytochrome Oxidase Subunits 1 and 2
Authors: Pusnik Mascha , Schneider André
Published: November 2011

The pentatricopeptide repeat (PPR) protein family consists of organellar proteins predicted to bind to specific RNA sequences. Plants have hundreds of distinct PPR proteins, whereas other eukaryotes generally have many fewer. The genome of the parasitic protozoon
Trypanosoma brucei
is predicted to encode more than 30 different PPR proteins, which is an extraordinarily high number for a nonplant organism. Here we report the characterization
T. brucei
PPR9 (TbPPR9). Epitope tagging shows that the protein is exclusively mitochondrially localized. Interestingly, while in induced RNA interference cell lines TbPPR9 is efficiently downregulated, the level of its mRNA is not affected. Ablation of TbPPR9 selectively abolishes oxidative but not mitochondrial substrate-level phosphorylation. The molecular basis of this phenotype is the fact that TbPPR9 is required for the stability of the cytochrome oxidase subunit 1 (COX1) and COX2 mRNAs. This is supported by the observation that ablation of TbPPR9 destabilizes the COX complex but not the cytochrome
bc
1
or the ATP synthase complex. Moreover, it was shown by blue native gel electrophoresis that TbPPR9 is present in a large complex of unknown composition.
Proteomic Analysis of Trichoderma atroviride Reveals Independent Roles for Transcription Factors BLR-1 and BLR-2 in Light and Darkness
Authors: Sánchez-Arreguín Alejandro , Pérez-Martínez Ana Silvia , Herrera-Estrella Alfredo
Published: November 2011

The genus
Trichoderma
is one of the most widely used biological control agents of plant-pathogenic fungi. The main mechanism for survival and dispersal of
Trichoderma
is through the production of asexual spores (conidia). The transition from filamentous growth to conidiation can be triggered by light, nutrient deprivation, and mechanical damage of the mycelium. We conducted proteomic profiling analyses of
Trichoderma atroviride
after a blue light pulse. The use of two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) analysis allowed us to identify 72 proteins whose expression was affected by blue light. Functional category analysis showed that the various proteins are involved in metabolism, cell rescue, and protein synthesis. We determined the relationship between mRNA levels of selected genes 30 min after a light pulse and protein expression levels at different times after the pulse and found this correlation to be very weak. The correlation was highest when protein and mRNA levels were compared for the same time point. The transcription factors BLR-1 and BLR-2 are vital to the photoconidiation process; here we demonstrate that both BLR proteins are active in darkness and affect several elements at both the transcript and protein levels. Unexpectedly, in darkness, downregulation of proteins prevailed in the Δ
blr-1
mutant, while upregulation of proteins predominated in the Δ
blr-2
mutant. Our data demonstrate that the BLR proteins play roles individually and as a complex.
Characterization of DNA Sequences Required for the CcrAB-Mediated Integration of Staphylococcal Cassette Chromosome
mec
, a Staphylococcus aureus Genomic Island
Authors: Wang Lei , Safo Martin , Archer Gordon L.
Published: November 2011

The mobile element staphylococcal cassette chromosome
mec
(SC
Cmec
), which carries
mecA
, the gene responsible for methicillin resistance in staphylococci, inserts into the chromosome at a specific site,
attB
, mediated by serine recombinases, CcrAB and CcrC, encoded on the element. This study sought to determine the sequence specificity for CcrB DNA binding
in vitro
and for CcrAB-mediated SCC
mec
insertion
in vivo
. CcrB DNA binding, as assessed
in vitro
by electrophoretic mobility shift assay (EMSA), revealed that a 14-bp sequence (
CGTATCATAAGTAA
; the terminal sequence of the
orfX
gene) was the minimal requirement for binding, containing an invariant sequence (
TATCATAA
) found in all chromosomal (
attB
) and SCC
mec
(
attS
) integration sites. The sequences flanking the minimal
attB
and
attS
binding sites required for insertion
in vivo
were next determined. A plasmid containing only 37 bp of
attS
and flanking sequences was required for integration into the
attB
site at 92% efficiency. In contrast, at least 200 bp of sequence within
orfX
, 5′ to the
attB
core, and 120 bp of specific sequence 3′ to the
orfX
stop site and
attB
core were required for the highest insertion frequency. Finally, an
attS
-containing plasmid was inserted into wild-type
Staphylococcus aureus
strains without integrated SCC
mec
(methicillin susceptible) at various frequencies which were determined both by sequences flanking the
att
site and by the presence of more than one
att
site on either the chromosome or the integration plasmid. This sequence specificity may play a role in the epidemiology of SCC
mec
acquisition.
Novel Roles of SoxR, a Transcriptional Regulator from
X
anthomonas campestris, in Sensing Redox-Cycling Drugs and Regulating a Protective Gene That Have Overall Implications for Bacterial Stress Physiology and Virulence on a Host Plant
Authors: Mahavihakanont Aekkapol , Charoenlap Nisanart , Namchaiw Poommaree , Eiamphungporn Warawan , Chattrakarn Sorayut , Vattanaviboon Paiboon , Mongkolsuk Skorn
Published: November 2011

In
Xanthomonas campestris
pv. campestris, SoxR likely functions as a sensor of redox-cycling drugs and as a transcriptional regulator. Oxidized SoxR binds directly to its target site and activates the expression of
xcc0300
, a gene that has protective roles against the toxicity of redox-cycling compounds. In addition, SoxR acts as a noninducible repressor of its own expression.
X. campestris
pv. campestris requires SoxR both for protection against redox-cycling drugs and for full virulence on a host plant. The
X. campestris
model of the gene regulation and physiological roles of SoxR represents a novel variant of existing bacterial SoxR models.
Network Identification and Flux Quantification of Glucose Metabolism in Rhodobacter sphaeroides under Photoheterotrophic H
2
-Producing Conditions
Authors: Tao Yongzhen , Liu Deng , Yan Xing , Zhou Zhihua , Lee Jeong K. , Yang Chen
Published: November 2011

The nonsulfur purple bacteria that exhibit unusual metabolic versatility can produce hydrogen gas (H
2
) using the electrons derived from metabolism of organic compounds during photoheterotrophic growth. Here, based on
13
C tracer experiments, we identified the network of glucose metabolism and quantified intracellular carbon fluxes in
Rhodobacter sphaeroides
KD131 grown under H
2
-producing conditions. Moreover, we investigated how the intracellular fluxes in
R. sphaeroides
responded to knockout mutations in hydrogenase and poly-β-hydroxybutyrate synthase genes, which led to increased H
2
yield. The relative contribution of the Entner-Doudoroff pathway and Calvin-Benson-Bassham cycle to glucose metabolism differed significantly in hydrogenase-deficient mutants, and this flux change contributed to the increased formation of the redox equivalent NADH. Disruption of hydrogenase and poly-β-hydroxybutyrate synthase resulted in a significantly increased flux through the phosphoenolpyruvate carboxykinase and a reduced flux through the malic enzyme. A remarkable increase in the flux through the tricarboxylic acid cycle, a major NADH producer, was observed for the mutant strains. The
in vivo
regulation of the tricarboxylic acid cycle flux in photoheterotrophic
R. sphaeroides
was discussed based on the measurements of
in vitro
enzyme activities and intracellular concentrations of NADH and NAD
+
. Overall, our results provide quantitative insights into how photoheterotrophic cells manipulate the metabolic network and redistribute intracellular fluxes to generate more electrons for increased H
2
production.
The Cyanobacterial NAD Kinase Gene
sll1415
Is Required for Photoheterotrophic Growth and Cellular Redox Homeostasis in Synechocystis sp. Strain PCC 6803
Authors: Gao Hong , Xu Xudong
Published: November 2011

NAD kinase (NADK), which phosphorylates NAD to NADP, is one of the key enzymes regulating the cellular NADP(H) level. In
Synechocystis
sp. strain PCC 6803,
slr0400
and
sll1415
were shown to encode NAD kinases. The NADP(H) pool in the cyanobacterium was remarkably reduced by an
sll1415
-null mutation but slightly reduced by an
slr0400
-null mutation. The reduction of the NADP(H) level in the
sll1415
mutant led to a significant accumulation of glucose-6-phosphate and a loss of photoheterotrophic growth. As the primary NADK gene,
sll1415
was found to inhibit the transcription of genes involved in redox homeostasis and to exert stronger effects on methyl viologen tolerance than
slr0040
.
BpsR Modulates Bordetella Biofilm Formation by Negatively Regulating the Expression of the Bps Polysaccharide
Authors: Conover Matt S. , Redfern Crystal J. , Ganguly Tridib , Sukumar Neelima , Sloan Gina , Mishra Meenu , Deora Rajendar
Published: November 2011

Bordetella
bacteria are Gram-negative respiratory pathogens of animals, birds, and humans. A hallmark feature of some
Bordetella
species is their ability to efficiently survive in the respiratory tract even after vaccination.
Bordetella bronchiseptica
and
Bordetella pertussis
form biofilms on abiotic surfaces and in the mouse respiratory tract. The Bps exopolysaccharide is one of the critical determinants for biofilm formation and the survival of
Bordetella
in the murine respiratory tract. In order to gain a better understanding of regulation of biofilm formation, we sought to study the mechanism by which Bps expression is controlled in
Bordetella
. Expression of
bpsABCD
(
bpsA-D
) is elevated in biofilms compared with levels in planktonically grown cells. We found that
bpsA-D
is expressed independently of BvgAS. Subsequently, we identified an open reading frame (ORF), BB1771 (designated here
bpsR
), that is located upstream of and in the opposite orientation to the
bpsA-D
locus. BpsR is homologous to the MarR family of transcriptional regulators. Measurement of
bpsA
and
bpsD
transcripts and the Bps polysaccharide levels from the wild-type and the Δ
bpsR
strains suggested that BpsR functions as a repressor. Consistent with enhanced production of Bps, the
bpsR
mutant displayed considerably more structured biofilms. We mapped the
bpsA-D
promoter region and showed that purified BpsR protein specifically bound to the
bpsA-D
promoter. Our results provide mechanistic insights into the regulatory strategy employed by
Bordetella
for control of the production of the Bps polysaccharide and biofilm formation.
Effects on Growth by Changes of the Balance between GreA, GreB, and DksA Suggest Mutual Competition and Functional Redundancy in Escherichia coli
Authors: Vinella Daniel , Potrykus Katarzyna , Murphy Helen , Cashel Michael
Published: November 2011

It is well known that ppGpp and DksA interact with bacterial RNA polymerase (RNAP) to alter promoter activity. This study suggests that GreA plays a major role and GreB plays a minor role in the ppGpp-DksA regulatory network. We present evidence that DksA and GreA/GreB are redundant and/or share similar functions: (i) on minimal medium GreA overproduction suppresses the growth defects of a
dksA
mutant; (ii) GreA and DksA overexpression partially suppresses the auxotrophy of a ppGpp-deficient strain; (iii) microarrays show that many genes are regulated similarly by GreA and DksA. We also find instances where GreA and DksA seem to act in opposition: (i) complete suppression of auxotrophy occurs by overexpression of GreA or DksA only in the absence of the other protein; (ii) P
gadA
and P
gadE
promoter fusions, along with many other genes, are dramatically affected
in vivo
by GreA overproduction only when DksA is absent; (iii) GreA and DksA show opposite regulation of a subset of genes. Mutations in key acidic residues of GreA and DksA suggest that properties seen here probably are not explained by known biochemical activities of these proteins. Our results indicate that the general pattern of gene expression and, in turn, the ability of
Escherichia coli
to grow under a defined condition are the result of a complex interplay between GreA, GreB, and DksA that also involves mutual control of their gene expression, competition for RNA polymerase binding, and similar or opposite action on RNA polymerase activity.
Voxel-based analysis of apparent diffusion coefficient in perihaematomal oedema: associated factors and outcome predictive value for intracerebral haemorrhage
Authors: Tsai Yuan-Hsiung , Hsu Li-Ming , Weng Hsu-Huei , Lee Ming-Hsueh , Yang Jen-Tsung , Lin Ching-Po
Published: November 2011

Objectives

The pathophysiology of perihaematomal oedema (PO) surrounding a primary intracerebral haemorrhage (ICH) is complicated and incompletely understood. We prospectively investigated the components of PO with voxel-based analysis of the apparent diffusion coefficient (ADC) value and assessed its predictive value for functional outcome.

Design

Forty-six patients with ICH who were enrolled for clinical evaluation underwent MRI scans within 24 h after ICH. Based on the ADC value of the ipsilateral voxels divided by the mean ADC value of the contralateral mirror region of interest, the voxels with oedema were classified into three categories: cytotoxic, vasogenic and undetermined. The percentages of cytotoxic and vasogenic oedema were then calculated and correlated with clinical outcome according to the modified Rankin Scale (mRS) at 6 months after ICH. The intraobserver and interobserver reliability of this method were examined using intraclass correlation coefficients.

Results

The intraclass correlation coefficients showed that analysis using the voxel-based method is highly reliable. Among the clinical variables tested, age and serum creatinine levels were positively correlated with percentage of cytotoxic oedema. Age, history of coronary artery disease, National Institutes of Health Stroke Scale score and percentage of cytotoxic oedema were all associated with mRS at 6 months after ICH.

Conclusions

The pathophysiological processes within PO are complicated. Voxel-based analysis of ADC values may help to identify the components of PO and may be beneficial for decision making and predicting outcome.
Management of patient adherence to medications: protocol for an online survey of doctors, pharmacists and nurses in Europe
Authors: Clyne Wendy , Mshelia Comfort , Hall Stephanie , McLachlan Sarah , Jones Peter , Dobbels Fabienne , Ruppar Todd , Siebens Kaat , Morrison Val , De Geest Sabina , Kardas Premyzlaw
Published: November 2011

Introduction

It is widely recognised that many patients do not take prescribed medicines as advised. Research in this field has commonly focused on the role of the patient in non-adherence; however, healthcare professionals can also have a major influence on patient behaviour in taking medicines. This study examines the perceptions, beliefs and behaviours of healthcare professionals—doctors, pharmacists and nurses—about patient medication adherence.

Methods and analysis

This paper describes the study protocol and online questionnaire used in a cross-sectional survey of healthcare professionals in Europe. The participating countries include Austria, Belgium, France, Greece, The Netherlands, Germany, Poland, Portugal, Switzerland, Hungary, Italy and England. The study population comprises primary care and community-based doctors, pharmacists and nurses involved in the care of adult patients taking prescribed medicines for chronic and acute illnesses.

Discussion

Knowledge of the nature, extent and variability of the practices of healthcare professionals to support medication adherence could inform future service design, healthcare professional education, policy and research.
Complex shaped detachable platinum coil system for the treatment of cerebral aneurysms: The Codman Trufill DCS and Trufill DCS Orbit Detachable Coil System COMPLEX Registry final results
Authors: Bendok Bernard R , Rahme Rudy J ,   for the Complex Registry Group*
Published: November 2011

Objective

To report on an electronic database with longitudinal information on the use of bare platinum coils for the endovascular occlusion of cerebral aneurysms. We report here the final analysis of the data.

Methods

From 1 May 2004 to 10 July 2007, a global registry was conducted at 36 centers in the USA, Europe and Latin America. 303 patients were enrolled, of whom 299 patients were treated with bare detachable platinum coils (mostly Trufill Detachable Coil System (DCS) Orbit coils). Short and long term anatomical and clinical data were collected. Logistic regression analysis was used to examine the association of selected patient characteristics to outcomes of recanalization and retreatment.

Results

313 aneurysms, ruptured and unruptured, were treated in the 299 patients. Follow-up data were available on 185 patients: 150 (81%) had a 3–6 month follow-up, 63 (34%) had a 1 year follow-up and five (3%) had a 2 year follow-up. This paper reviews the status of 185 patients with follow-up data available at this time. Immediately postprocedure, 114 (58%) aneurysms were completely obliterated, 40 (20%) residual neck, 23 (12%) residual aneurysm and 19 (10%) dog ear. Of 174 aneurysms in 167 patients with angiographic follow-up, 137 (79%) remained stable or improved, nine (5%) showed aneurysm regrowth, 26 (15%) showed compaction and two (1%) had migrated. At 3–6 months, 11 of the 174 (6%) aneurysms were re-treated.

Conclusion

These results confirm previous outcome data of endovascular occlusion of cerebral aneurysms with Trufill DCS Orbit complex shaped detachable platinum coils. Complications related to the device were rare.
Electromechanical feedback with reduced cellular connectivity alters electrical activity in an infarct injured left ventricle: a finite element model study
Authors: Wall Samuel T. , Guccione Julius M. , Ratcliffe Mark B. , Sundnes Joakim S.
Published: November 2011

Myocardial infarction (MI) significantly alters the structure and function of the heart. As abnormal strain may drive heart failure and the generation of arrhythmias, we used computational methods to simulate a left ventricle with an MI over the course of a heartbeat to investigate strains and their potential implications to electrophysiology. We created a fully coupled finite element model of myocardial electromechanics consisting of a cellular physiological model, a bidomain electrical diffusion solver, and a nonlinear mechanics solver. A geometric mesh built from magnetic resonance imaging (MRI) measurements of an ovine left ventricle suffering from a surgically induced anteroapical infarct was used in the model, cycled through the cardiac loop of inflation, isovolumic contraction, ejection, and isovolumic relaxation. Stretch-activated currents were added as a mechanism of mechanoelectric feedback. Elevated fiber and cross fiber strains were observed in the area immediately adjacent to the aneurysm throughout the cardiac cycle, with a more dramatic increase in cross fiber strain than fiber strain. Stretch-activated channels decreased action potential (AP) dispersion in the remote myocardium while increasing it in the border zone. Decreases in electrical connectivity dramatically increased the changes in AP dispersion. The role of cross fiber strain in MI-injured hearts should be investigated more closely, since results indicate that these are more highly elevated than fiber strain in the border of the infarct. Decreases in connectivity may play an important role in the development of altered electrophysiology in the high-stretch regions of the heart.
Differential effect of atorvastatin and tacrolimus on proliferation of vascular smooth muscle and endothelial cells
Authors: Giordano Arturo , Romano Simona , Monaco Mario , Sorrentino Antonio , Corcione Nicola , Di Pace Anna Laura , Ferraro Paolo , Nappo Giovanna , Polimeno Michele , Romano Maria Fiammetta
Published: November 2011

Although considered promising for use in drug-eluting stents (DES), tacrolimus failed clinically. Tacrolimus inhibits growth factor production but can also act as a growth factor on vascular smooth muscle cells (VSMC). This unexpected proliferative stimulus could reverse the beneficial effects of the drug on restenosis. We hypothesized that tacrolimus' association with statins, which lower cholesterol and impair cell proliferation, could restore tacrolimus' beneficial effect by abrogating the aberrant proliferative stimulus. Additionally, since maintenance of endothelial function represents a challenge for new-generation DES, we investigated the combined effect of tacrolimus and atorvastatin on endothelial cells. Human VSMC and umbilical vein endothelial cells (HUVEC) were incubated with 100 nM tacrolimus and increasing doses of atorvastatin (0–3.0 μM). Atorvastatin plus tacrolimus dose-dependently inhibited VSMC proliferation. The percentage of cells incorporating 5-bromo-2′-deoxyuridine (BrdU) in their DNA was 49 ± 14% under basal conditions, 62 ± 15% ( P = 0.01) with tacrolimus, 40 ± 22% with 3 μM atorvastatin, and 30 ± 7% ( P < 0.05) with 3 μM atorvastatin plus tacrolimus. Atorvastatin downregulated β-catenin, Erk1 and Erk2, and cyclin B in tacrolimus-stimulated VSMC. In contrast, atorvastatin plus tacrolimus did not affect proliferation of endothelial cells. The percentage of HUVEC incorporating BrdU in their DNA was 47 ± 8% under basal conditions, 58 ± 6% ( P = 0.01) with tacrolimus, 45 ± 4% with 3 μM atorvastatin, and 49 ± 1% with 3 μM atorvastatin plus tacrolimus. Both agents stimulated endoglin production by HUVEC. Taken together, these results suggest that, when combined with tacrolimus, atorvastatin exerts a dose-dependent antiproliferative effect on VSMC. In contrast, atorvastatin acts in concert with tacrolimus in HUVEC to stimulate production of endoglin, a factor that has an important role in endothelial repair. Our study supports the conclusion that prevention of postcoronary in-stent restenosis and late thrombosis may benefit of concomitant association of tacrolimus and high doses of atorvastatin.
Molecular chaperones and heat shock proteins in atherosclerosis
Authors: Xu Qingbo , Metzler Bernhard , Jahangiri Marjan , Mandal Kaushik
Published: November 2011

In response to stress stimuli, mammalian cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs). HSPs are a family of proteins serving as molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. Physiologically, HSPs play a protective role in the homeostasis of the vessel wall but have an impact on immunoinflammatory processes in pathological conditions involved in the development of atherosclerosis. For instance, some members of HSPs have been shown to have immunoregulatory properties and modification of innate and adaptive response to HSPs, and can protect the vessel wall from the disease. On the other hand, a high degree of sequence homology between microbial and mammalian HSPs, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. Furthermore, HSPs and anti-HSP antibodies have been shown to elicit production of proinflammatory cytokines. Potential therapeutic use of HSP in prevention of atherosclerosis involves achieving optimal balance between protective and immunogenic effects of HSPs and in the progress of research on vaccination. In this review, we update the progress of studies on HSPs and the integrity of the vessel wall, discuss the mechanism by which HSPs exert their role in the disease development, and highlight the potential clinic translation in the research field.