bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic incentives for sustainable resource consumption at a large university – Past performance and future considerations
Authors: Levy Jonathan I. , Dilwali Kumkum M.
Published: July 2006

Colleges and universities that are interested in reducing their environmental impacts are faced with the difficulties of providing incentives for sustainable behavior and attempting to quantify the gains that policies would provide. In this paper, we use a case study to demonstrate the benefits as well as the difficulties encountered with one type of incentive program, a revolving loan fund. During the five‐year tenure of the case study fund, the program yielded a 34 percent return on conservation investments, with associated decreases in resource usage, ambient air emissions, and water consumption. Using a past damage function study, we estimate that the reduced emissions result in over US$100,000 of avoided environmental externalities per year. Although the economic returns and environmental benefits were significant, participation declined rapidly after the initial rollout of the program and relatively non‐technical conservation measures were generally the focus of projects. Through surveys of both participating and non‐participating facility directors, we determined that lack of knowledge of effective conservation measures and limitations in staff availability were the key barriers preventing more extensive participation. Increased flow of information, through such actions as frequent facility director correspondence and independent energy audits of facilities, would be likely to encourage sustainable resource consumption in future applications of revolving loan funds and other campus greening efforts.
How satisfied are academics with their primary tasks of teaching, research and administration and management?
Authors: Oshagbemi Titus
Published: July 2006

Higher education (HE) is currently undergoing changes and facing challenges in the UK, including coping with growth in the mature student entry, the removal of the binary divide, the reduction of student grants and the likelihood that students will increasingly have to pay more for their education. This article reflects on sustainable development in HE and probes how satisfied academics are with their primary tasks of teaching, research and administration and management. Using a questionnaire survey, the study found that about 65 percent of the university teachers were satisfied, very satisfied or extremely satisfied with research. Similar figures for teaching and administration and management are about 80 and 40 percent respectively. The study further investigated operational aspects of universities and in particular, whether satisfaction with each of their core tasks was related to age, gender or rank. The results show that significant associations exist between age and satisfaction in the core aspects of the university teachers’ job. However the nature of the impact of age on the job satisfaction of academics varies from one aspect of the job to another. The nature of the relationships between age and research, teaching and administration and management is not clear, although the relationships themselves are statistically significant. While it appears that, generally, the older one is, the greater the satisfaction enjoyed with respect to teaching and administration and management, the reverse appears to be true with research satisfaction. The results also reveal, expectedly, that research satisfaction was related to rank – the higher the rank, the greater the level of research satisfaction. It was also found that gender satisfaction is not related to teaching, research or administration and management. The interpretations of these results and their implications to sustainability in higher education institutions are explored.
Sustainability management in campus housing
Authors: Shriberg Michael
Published: July 2006

Summarizes a study which provides a framework upon which to base management for sustainability in the University of Michigan’s Housing Division. Discusses three reasons why organizations should be interested in pursuing sustainability management: morality and intergenerational equity; survival; and organizational benefits and risks. Proposes a sustainability mission statement for Housing and assesses five operational areas and six decision‐making areas in terms of environmental impact (specific audit data are presented) and prospects for sustainability management. Presents summaries of all findings, as well as more detailed descriptions of dining and staffing assessments. Concludes that management for sustainability must be holistic, systemic and integrative. Major recommendations include appointing a sustainability coordinator and/or task group; conducting sustainability audits; training staff on sustainability; using full‐cost accounting and life‐cycle assessment as decision‐making tools; creating an environmental procurement program; forming a sustainable dining team; involving outside entities in sustainability efforts; and developing partnerships for material reuse.
Environmental management systems at North American universities
Authors: Herremans Irene , Allwright David E.
Published: July 2006

The purpose of this study is to determine what initiatives have been undertaken by universities across North America in implementing environmental management systems (EMS). Many universities have discovered that their activities can have significant impacts on the environment. As a result, some institutions have implemented systems to help them organize activities in order to recognize and reduce adverse environmental effects. This paper contributes to our understanding of these systems. A framework is developed that identifies important characteristics of effective EMS currently in use at some North American universities. The framework also provides guidance for those universities that have not yet developed effective EMS.
Sustainability: a new paradigm for industrial production
Authors: Gutberlet Jutta
Published: July 2006

Briefly discusses the industrial development process in Brazil by highlighting a few examples of its social and environmental implications. The current environmental crisis for which the industrial sector is co‐responsible puts evidence on the existing links between production and consumption cycles. In order to identify impacts at their origin, production processes and products need to be re‐assessed. Proposes a paradigm shift with the corporate world internalising the sustainability concept based on dematerialisation (tendency to use less material and energy inputs per unit of output) and eco‐efficiency (strategy to provide goods and services while continuously reducing ecological impacts).
Sustainability in teacher training courses in a sample of German universities
Authors: Henze Christa
Published: July 2006

This paper presents the main results of a recently completed empirical research project that focused on the concept of a sustainable development dimension in the context of teacher training courses at universities in the state of Northrhine‐Westphalia, Germany. In addition, some measures aimed at supporting the implementation and dissemination of the task of a sustainable development in higher education are suggested.
Sustainable living – Strategies for breaking the cycle of work and spend
Authors: Simon‐Brown Viviane
Published: July 2006

Consumerism is skyrocketing in the USA. This paper assists land‐grant university National Cooperative Research Extension Education Service (NCREES) faculty in understanding the definition of a consumer society, the dynamics of consumption patterns, the factors and values of sustainable economics, and the varying interpretations of consumer characteristics. It then identifies possible target populations, and suggests educational strategy options to be used to foster sustainable lifestyles and responsible consumer decisions. The strategies, which encompass NCREES disciplines, include a quality of life questioning system; redefining the relationship between job and social status; economics coursework; LETS education; time management and simple living workshops; acting as conduits to other programs; and most importantly, modeling sustainable behaviors. These are all important components of the sustainability formula and indicate some areas where universities could be more pro‐active.
Using Reuters 3000 Xtra system for financial information education
Authors: Liu Lewis G. , Holowczak Richard
Published: July 2006

Reuters 3000 Xtra is a real‐time and interactive global news and financial information service that covers the equity market, bond market, foreign currency and money market, and various derivative markets. While there are hundreds of business schools in the USA, only a handful of schools have established real‐time financial and trading services for educational purposes. Currently only six schools are equipped with such services in the USA. The Subotnick Financial Services Center at the Zicklin School of Business of the City University of New York is the only real‐time trading facility for education in New York City. Given the many advantages of educating and training students using simulation of real‐time trading, the number of business schools that are considering acquiring such services is bound to increase. The emerging issue is how to use services such as Reuters 3000 Xtra to provide financial information education for students, faculty members, and potential traders. This article covers some important features of Reuters 3000 Xtra and illustrates how it may be used to provide financial information education. This article specifically discusses the use of Reuters Instruction Code (RIC), Speed Guide, Model Browser, and PowerPlus Pro to access, retrieve, organise, display, and analyse real‐time data. Furthermore, this article demonstrates taking advantage of the real‐time data feed to test the portfolio diversification theory by developing a diversified portfolio in the equity market. It is our hope that students, faculty members, business librarians, business information specialists and financial portfolio managers who are involved in Reuters 3000 Xtra training and teaching will benefit from this article.
General practitioner non‐principals benefit from flexible working
Authors: French Fiona , Andrew Jane , Awramenko Morag , Coutts Helen , Leighton‐Beck Linda , Mollison Jill , Needham Gillian , Scott Anthony , Walker Kim
Published: July 2006

Purpose

The purpose of this study is to explore non‐principals’ working patterns and attitudes to work.

Design/methodology/approach

The article is based on data provided by a questionnaire survey.

Findings

Gender division was apparent among the non‐principals. Males were more likely to work full‐time, because their spouses modified their working hours.

Research limitations/implications

It was impossible to identify all non‐principals in Scotland or to compare responders and non‐responders, due to the lack of official data. Hence, the results might not be representative.

Practical implications

More flexible posts would enable GPs to more easily combine paid work with family commitments. It is anticipated that the new GP contract should deliver this.

Originality/value

This was the first time a study of all non‐principals in Scotland had been attempted. The findings provide a more comprehensive picture of GPs in Scotland and provide valuable information for policymakers.
Developing an evidence base for patient and public involvement
Authors: Murie Jill , Douglas‐Scott Gerrie
Published: July 2006

This paper summarises five years' experience of patient and public involvement in primary care, citing examples from the Lanark practice and Clydesdale Local Health Care Co‐operative (LHCC) in Lanarkshire, Scotland. Strategic development and models which align primary care structures within a framework for patient and public involvement are described, along with barriers to implementation. Examples derived from clinical governance, health promotion and needs assessment include patient and carer involvement in significant event analysis and audit, joint training and patient‐held record cards. Positive outcomes reported are effective dialogue between health professionals, patients and the public, service developments and quality improvements. The success of initiatives is retrospectively assessed against the Audit Commission's critical success factors.
Generation of α‐dense curves in a cube of IRn
Authors: Ziadi A. , Cherruault Y.
Published: July 2006

A multi‐dimensional global optimization method has been developed. This method uses the curves of IRn called α‐dense. A characterization of α‐dense curves is given in terms of γ‐stochastically independent functions as well as a constructive method to generate them by means of only one function φ called γ‐uniformly distributed has been developed. A very large class of functions which generate α‐dense curves is discussed. This class contains the γ‐uniformly distributed functions, the periodic functions and even functions which are not periodic, but which fulfil some properties.
Quality standards in drug and medical information departments
Authors: Khan Sadia , Bawden David
Published: July 2006

Quality standards in the enquiry answering function of health service drug information units and of pharmaceutical industry medical information departments are studied by an interview/questionnaire survey. Factors examined include the use of standardised and documented procedures, adherence to published guidelines, methods of evaluating quality, and the impact of ISO 9000 certification.
Professor Bernal’s ‘insidious and cavalier proposals’: the Royal Society scientific information conference, 1948
Authors: East Harry
Published: July 2006

For the 1948 Royal Society Conference, J.D. Bernal submitted a paper which proposed a provisional scheme for the central distribution of scientific papers. This provoked such a hostile and extreme reaction from both the learned society publishers and the national press that the paper was withdrawn in advance of the conference. It is extant in its Proceedings. This paper outlines the nature of the proposals, together with some contemporary reactions. Bernal‘s scheme certainly implied a revolutionary transformation of the status quo. However, his well‐known political beliefs probably played as instrumental a part in their rejection as the nature of the proposals themselves.
THE IMPACT OF RENT CONTROLS IN NON‐WALRASIAN MARKETS: AN AGENT‐BASED MODELING APPROACH
Authors: Bradburd Ralph , Sheppard Stephen , Bergeron Joseph , Engler Eric
Published: July 2006

ABSTRACT We use agent‐based models to consider rent ceilings in non‐Walrasian housing markets, where bargaining between landlord and tenant leads to exchange at a range of prices. In the non‐Walrasian setting agents who would be extramarginal in the Walrasian setting frequently are successful in renting, and actually account for a significant share of the units rented. This has several implications. First, rent ceilings above the Walrasian equilibrium price (WEP) can affect the market outcome. Second, rent ceilings that reduce the number of units rented do not necessarily reduce total market surplus. Finally, the distributional impact of rent controls differs from the Walrasian setting.
Dependence in the 2001 One-Number Census Project
Authors: Brown James , Abbott Owen , Diamond Ian
Published: July 2006

The one-number census approach was developed by the Office for National Statistics to adjust the counts from the 2001 census of England and Wales for underenumeration. The method is underpinned by an assumption of independence between the count of the population that was given by the 2001 census and the count that was given by the Census Coverage Survey. Some dependence was, however, detected, and the paper describes the strategy that was used to measure dependence and to adjust the 2001 census population estimates.
Haar–Fisz Estimation of Evolutionary Wavelet Spectra
Authors: Fryzlewicz Piotr , Nason Guy P.
Published: July 2006

We propose a new ‘Haar–Fisz’ technique for estimating the time-varying, piecewise constant local variance of a locally stationary Gaussian time series. We apply our technique to the estimation of the spectral structure in the locally stationary wavelet model. Our method combines Haar wavelets and the variance stabilizing Fisz transform. The resulting estimator is mean square consistent, rapidly computable and easy to implement, and performs well in practice. We also introduce the ‘Haar–Fisz transform’, a device for stabilizing the variance of scaled χ2-data and bringing their distribution close to Gaussianity.
Estimation of a Two-Equation Panel Model with Mixed Continuous and Ordered Categorical Outcomes and Missing Data
Authors: Spiess Martin
Published: July 2006

The paper proposes an estimation approach for panel models with mixed continuous and ordered categorical outcomes based on generalized estimating equations for the mean and pseudoscore equations for the covariance parameters. A numerical study suggests that efficiency can be gained in the mean parameter estimators by using individual covariance matrices in the estimating equations for the mean parameters. The approach is applied to estimate the returns to occupational qualification in terms of income and perceived job security in a 9-year period based on the German Socio-Economic Panel. To compensate for missing data, a combined multiple imputation–weighting approach is adopted.
Surface modification of wool fabric for printing with acid and reactive dyes
Authors: Kantouch A , Kantouch F , El‐Sayed H
Published: July 2006

The present study investigates environmentally safe pretreatments for wool fabric to improve its printing with acid and reactive dyes. Wool fabric was pretreated either with activated hydrogen peroxide using tetraacetylethylenediamine or with lipase enzyme under specified conditions. Some acid and reactive dyes were applied for wool printing using normal techniques. These treatments were found to improve the colour intensity of the printed fabrics to a level comparable with those of prechlorinated wool fabrics.
High affinity, high efficiency fibre‐reactive dyes
Authors: Smith Brent , Berger Rebecca , Freeman Harold S
Published: July 2006

A straightforward two‐step method for modifying commercial dichlorotriazine‐based fibre‐reactive dyes prior to their use in the dyeing process can greatly improve affinity and fixation efficiency on cotton, and reduce the salt requirements. The modification used in this study involved prereacting the commercial dyes with either cysteine or cysteamine followed by reaction of the resulting intermediate with cyanuric chloride. Cotton fabric dyed with the modified dyes had technical properties that were essentially equal to those obtained from the unmodified commercial dyes.
Dopaquinone redox exchange with dihydroxyindole and dihydroxyindole carboxylic acid
Authors: Edge R. , D'Ischia M. , Land E. J. , Napolitano A. , Navaratnam S. , Panzella L. , Pezzella A. , Ramsden C. A. , Riley P. A.
Published: July 2006

A pulse radiolytic investigation has been conducted to establish whether a redox reaction takes place between dopaquinone and 5,6‐dihydroxyindole (DHI) and its 2‐carboxylic acid (DHICA) and to measure the rate constants of the interactions. To obviate possible confounding reactions, such as nucleophilic addition, the method employed to generate dopaquinone used the dibromide radical anion acting on dopa to form the semiquinone which rapidly disproportionates to dopaquinone. In the presence of DHI the corresponding indole‐5,6‐quinone (and/or tautomers) was also formed directly but, by judicious selection of suitable relative concentrations of initial reactants, we were able to detect the formation of additional indolequinone from the redox exchange reaction of DHI with dopaquinone which exhibited a linear dependency on the concentration of DHI. Computer simulation of the experimental time profiles of the absorption changes showed that, under the conditions chosen, redox exchange does proceed but not quite to completion, a forward rate constant of 1.4 × 106/M/s being obtained. This is in the same range as the rate constants previously established for reactions of dopaquinone with cyclodopa and cysteinyldopa. In similar experiments carried out with DHICA, the reaction more obviously does not go to completion and is much slower, k (forward) =1.6 × 105/M/s. We conclude that, in the eumelanogenic pathway, DHI oxidation may take place by redox exchange with dopaquinone, although such a reaction is likely to be less efficient for DHICA.
Does fluoride rinsing have an effect on teeth status? Evaluation of preventive dental health activities for the youth of Woudenberg, The Netherlands
Authors: Pieterse S , De Jong N , De Vos N
Published: July 2006

Abstract:  Surveys among primary school children of group 8 (mainly 12‐year olds) in 1988/1989 and 1995/1996 revealed that the dental status in Woudenberg was worse than in other municipalities in the Eemland region. Therefore, several dental preventive activities were started in Woudenberg for children aged 0–12 years. This included fluoride rinsing and teeth brushing lessons at primary schools. So as to evaluate the effect of these school activities, a new survey was carried out in Woudenberg in 2004. The teeth status (DMF‐S value, percentage sound teeth, percentage erosion) was investigated by examination. Information regarding dental hygiene behaviour and participation in teeth brushing lessons was obtained by questionnaire. Teeth status (measured by DMF‐S value as well as percentage sound teeth) at rinsing schools in 2004 was significantly better than at the same schools in 1995/1996. Multivariate analyses revealed that fluoride rinsing for at least 3 years (besides educational level of parents) is the most determining factor for teeth status independent of other variables. Pupils who never rinsed with fluoride were almost four times more likely to have caries lesions than pupils who rinsed for at least 3 years. This study strongly indicates that long‐term rinsing with fluoride has a positive effect on teeth status.
AparAHomolog Selectively Influences Positioning of the Large Chromosome Origin inVibrio cholerae
Authors: Saint-Dic Djenann , Frushour Brian P. , Kehrl Jason H. , Kahng Lyn Sue
Published: July 2006

AVibrio choleraedeletion mutant lacking VS2773, aparApartitioning gene homolog located in aparABoperon on the large chromosome, displays altered positioning of the large chromosome origin. Deletion of a secondparAhomolog on the large chromosome (VC2061) does not affect its origin positioning. The origin position of the small chromosome is unchanged by either or both of these deletions, suggesting that VC2773 function is specific to the replicon on which it is carried. VC2773 and VC2772 form aparABSsystem with inverted repeats found near the large chromosome origin.
UvrD Helicase Suppresses Recombination and DNA Damage-Induced Deletions
Authors: Kang Josephine , Blaser Martin J.
Published: July 2006

UvrD, a highly conserved helicase involved in mismatch repair, nucleotide excision repair (NER), and recombinational repair, plays a critical role in maintaining genomic stability and facilitating DNA lesion repair in many prokaryotic species. In this report, we focus on the UvrD homolog in
Helicobacter pylori
, a genetically diverse organism that lacks many known DNA repair proteins, including those involved in mismatch repair and recombinational repair, and that is noted for high levels of inter- and intragenomic recombination and mutation.
H. pylori
contains numerous DNA repeats in its compact genome and inhabits an environment rich in DNA-damaging agents that can lead to increased rearrangements between such repeats. We find that
H. pylori
UvrD functions to repair DNA damage and limit homologous recombination and DNA damage-induced genomic rearrangements between DNA repeats. Our results suggest that UvrD and other NER pathway proteins play a prominent role in maintaining genome integrity, especially after DNA damage; thus, NER may be especially critical in organisms such as
H. pylori
that face high-level genotoxic stress in vivo.
Identification and Characterization of Bacterial Cysteine Dioxygenases: a New Route of Cysteine Degradation for Eubacteria
Authors: Dominy John E. , Simmons Chad R. , Karplus P. Andrew , Gehring Amy M. , Stipanuk Martha H.
Published: July 2006

In metazoa and fungi, the catabolic dissimilation of cysteine begins with its sulfoxidation to cysteine sulfinic acid by the enzyme cysteine dioxygenase (CDO). In these organisms, CDO plays an important role in the homeostatic regulation of steady-state cysteine levels and provides important oxidized metabolites of cysteine such as sulfate and taurine. To date, there has been no experimental evidence for the presence of CDO in prokaryotes. Using PSI-BLAST searches and crystallographic information about the active-site geometry of mammalian CDOs, we identified a total of four proteins from
Bacillus subtilis
,
Bacillus cereus
, and
Streptomyces coelicolor
A3(2) that shared low overall identity to CDO (13 to 21%) but nevertheless conserved important active-site residues. These four proteins were heterologously expressed and purified to homogeneity by a single-step immobilized metal affinity chromatography procedure. The ability of these proteins to oxidize cysteine to cysteine sulfinic acid was then compared against recombinant rat CDO. The kinetic data strongly indicate that these proteins are indeed bona fide CDOs. Phylogenetic analyses of putative bacterial CDO homologs also indicate that CDO is distributed among species within the phyla of
Actinobacteria
,
Firmicutes
, and
Proteobacteria
. Collectively, these data suggest that a large subset of eubacteria is capable of cysteine sulfoxidation. Suggestions are made for how this novel pathway of cysteine metabolism may play a role in the life cycle of the eubacteria that have it.
Sau1: a Novel Lineage-Specific Type I Restriction-Modification System That Blocks Horizontal Gene Transfer into
Staphylococcus aureus
and between
S. aureus
Isolates of Different Lineages
Authors: Waldron Denise E. , Lindsay Jodi A.
Published: July 2006

The Sau1 type I restriction-modification system is found on the chromosome of all nine sequenced strains of
Staphylococcus aureus
and includes a single
hsdR
(restriction) gene and two copies of
hsdM
(modification) and
hsdS
(sequence specificity) genes. The strain
S. aureus
RN4220 is a vital intermediate for laboratory
S. aureus
manipulation, as it can accept plasmid DNA from
Escherichia coli
. We show that it carries a mutation in the
sau1hsdR
gene and that complementation restored a nontransformable phenotype. Sau1 was also responsible for reduced conjugative transfer from enterococci, a model of vancomycin resistance transfer. This may explain why only four vancomycin-resistant
S. aureus
strains have been identified despite substantial selective pressure in the clinical setting. Using a multistrain
S. aureus
microarray, we show that the two copies of sequence specificity genes (
sau1hsdS1
and
sau1hsdS2
) vary substantially between isolates and that the variation corresponds to the 10 dominant
S. aureus
lineages. Thus, RN4220 complemented with
sau1hsdR
was resistant to bacteriophage lysis but only if the phage was grown on
S. aureus
of a different lineage. Similarly, it could be transduced with DNA from its own lineage but not with the phage grown on different
S. aureus
lineages. Therefore, we propose that Sau1 is the major mechanism for blocking transfer of resistance genes and other mobile genetic elements into
S. aureus
isolates from other species, as well as for controlling the spread of resistance genes between isolates of different
S. aureus
lineages. Blocking Sau1 should also allow genetic manipulation of clinical strains of
S. aureus
.
No Single Irreplaceable Acidic Residues in the
Escherichia coli
Secondary Multidrug Transporter MdfA
Authors: Sigal Nadejda , Molshanski-Mor Shahar , Bibi Eitan
Published: July 2006

The largest family of solute transporters (major facilitator superfamily [MFS]) includes proton-motive-force-driven secondary transporters. Several characterized MFS transporters utilize essential acidic residues that play a critical role in the energy-coupling mechanism during transport. Surprisingly, we show here that no single acidic residue plays an irreplaceable role in the
Escherichia coli
secondary multidrug transporter MdfA.
Lipoprotein Multigene Families in
Mycoplasma pneumoniae
Authors: Hallamaa K. M. , Browning G. F. , Tang S. L.
Published: July 2006

In this study, reverse transcriptase PCR was employed to construct a
transcriptional profile of
Mycoplasma pneumoniae
lipoprotein genes contained in six multigene families. Most genes were
found to be expressed. Many truncated lipoprotein genes were expressed,
often polycistronically with other truncated genes, indicating that
these genes may still be
functional.
Chronic bronchitis and urban air pollution in an international study
Authors: Sunyer J , Jarvis D , Gotschi T , Garcia-Esteban R , Jacquemin B , Aguilera I , Ackerman U , de Marco R , Forsberg B , Gislason T , Heinrich J , Norbäck D , Villani S , Künzli N
Published: July 2006

Objectives:The chronic effects of urban air pollution are not well known. The authors’ aim was to investigate the association between the prevalence and new onset of chronic bronchitis and urban air pollution.

Methods:Subjects from the general population randomly selected for the European Community Respiratory Health Survey (ECRHS I) during 1991–93 in 21 centres in 10 countries were followed up from the years 2000 to 2002 (n = 3232 males and 3592 females; average response rate = 65.3%). PM2.5and elements, with the same equipment at centre level, and home outdoor NO2in 1634 individuals were measured. Hierarchical models were used.

Results:The prevalence and new onset of chronic phlegm during follow up were 6.9% and 4.5%, respectively, 5.3% in males and 3.5% in females. Smoking, rhinitis, poor education, and low social class were associated with (prevalence and new onset of) chronic phlegm in both genders, and occupational exposures in males and traffic intensity (adjusted odds ratio for constant traffic, OR = 1.86; 95% CI 1.24 to 2.77) as well as home outdoor NO2(OR > 50 μg/m3v< 20μg3 =  2.71; 95% CI 1.03 to 7.16) among females. PM2.5and S content at centre level did not show any association with prevalence or new onset of chronic phlegm. Similar results were obtained with chronic productive cough.

Conclusion:Individual markers of traffic at household level such as reported intensity and outdoor NO2were risk factors for chronic bronchitis among females.
Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model
Authors: Alwayn Ian P. J. , Andersson Charlotte , Lee Sang , Arsenault Danielle A. , Bistrian Bruce R. , Gura Kathleen M. , Nose Vania , Zauscher Blanca , Moses Marsha , Puder Mark
Published: July 2006

Steatosis is a prominent feature of nonalcoholic fatty liver disease and a potential promoter of inflammation. Injury leading to cirrhosis is partly mediated by dysregulation of matrix protein turnover. Matrix metalloproteinase (MMP) inhibitors protect mice from lethal TNF-α induced liver injury. We hypothesized that Marimastat, a broad-spectrum MMP and TNF-α converting enzyme (TACE) inhibitor, might modulate this injury through interruption of inflammatory pathways. Triglyceride and phospholipid levels (liver, serum) and fatty acid profiles were used to assess essential fatty acid status and de novo lipogenesis as mechanisms for hepatic steatosis. Mice receiving a fat-free, high-carbohydrate diet (HCD) for 19 days developed severe fatty liver infiltration, demonstrated by histology, magnetic resonance spectroscopy, and elevated liver function tests. Animals receiving HCD plus Marimastat (HCD+MAR) were comparable to control animals. Increased tissue levels of peroxisome proliferator activated receptor-α (PPAR-α), higher levels of serum IL-6, and decreased levels of serum TNF-α receptor II were also seen in the HCD+MAR group compared with HCD-only. In addition, there was increased phosphorylation, and likely activation, of PPAR-α in the HCD+MAR group. PPAR-α is a transcription factor involved in β-oxidation of fatty acids, and IL-6 is a hepatoprotective cytokine. Liver triglyceride levels were higher and serum triglyceride and phospholipid levels lower with HCD-only but improved with Marimastat treatment. HCD-only and HCD+MAR groups were essential fatty acid deficient and had elevated rates of de novo lipogenesis. We therefore conclude that Marimastat reduces liver triglyceride accumulation by increasing fat oxidation and/or liver clearance of triglycerides. This may be related to increased expression and activation of PPAR-α or IL-6, respectively.
Mice with experimental colitis show an altered metabolism with decreased metabolic rate
Authors: Melgar Silvia , Bjursell Mikael , Gerdin Anna-Karin , Svensson Lennart , Michaëlsson Erik , Bohlooly-Y Mohammad
Published: July 2006

Patients with inflammatory bowel disease (IBD) suffer from body weight loss, malnutrition, and several other metabolic alterations affecting their quality of life. The aim of this study was to investigate the metabolic changes that may occur during acute and chronic colonic inflammation induced by dextran sulfate sodium (DSS) in mice. Clinical symptoms and inflammatory markers revealed the presence of an ongoing inflammatory response in the DSS-treated mice. Mice with acute inflammation had decreased body weight, respiratory exchange ratios (RER), food intake, and body fat content. Mice with chronic inflammation had decreased nutrient uptake, body fat content, locomotor activity, metabolic rates, and bone mineral density. Despite this, the body weight, food and water intake, lean mass, and RER of these mice returned to values similar to those in healthy controls. Thus, murine experimental colitis is associated with significant metabolic alterations similar to IBD patients. Our data show that the metabolic responses during acute and chronic inflammation are different, although the metabolic rate is reduced in both phases. These observations suggest compensatory metabolic alterations in chronic colitis resulting in a healthy appearance despite gross colon pathology.
TLRs in the Gut I. The role of TLRs/Nods in intestinal development and homeostasis
Authors: Sanderson Ian R. , Walker W. Allan
Published: July 2006

The innate immune system includes microbial pattern recognition receptors that detect bacteria and viral products at the cell surface, in vesicles, and within the cytoplasm. Transmembrane signaling occurs through Toll-like receptors (TLRs). Cytoplasmic receptors are generally members of the nucleotide-binding domain (NOD)-leucine-rich repeat (LRR) family (CATERPILLER family). They influence the effects of other family members and of TLRs. Most NOD-LRR members enhance signal transduction, but Monarch-1 counterbalances TLR activity. NOD-LRR family members also act within the adaptive immune system. The class II transactivator regulates major histocompatibility complex class II expression. In the intestine, it is developmentally regulated, and its expression depends on weaning and, independently, on age.
Empirical and theoretical analysis of the extremely low frequency arterial blood pressure power spectrum in unanesthetized rat
Authors: Brown David R. , Cassis Lisa A. , Silcox Dennis L. , Brown Laura V. , Randall David C.
Published: July 2006

The slope of the log of power versus the log of frequency in the arterial blood pressure (BP) power spectrum is classically considered constant over the low-frequency range (i.e., “fractal” behavior), and is quantified by β in the relationship “1/ fβ.” In practice, the fractal range cannot extend to indefinitely low frequencies, but factor(s) that terminate this behavior, and determine β, are unclear. We present 1) data in rats ( n = 8) that reveal an extremely low frequency spectral region (0.083–1 cycle/h), where β approaches 0 (i.e., the “shoulder”); and 2) a model that 1) predicts realistic values of β within that range of the spectrum that conforms to fractal dynamics (∼1–60 cycles/h), 2) offers an explanation for the shoulder, and 3) predicts that the “successive difference” in mean BP (mBP) is an important parameter of circulatory function. We recorded BP for up to 16 days. The absolute difference between successive mBP samples at 0.1 Hz (the successive difference, or Δ) was 1.87 ± 0.21 mmHg (means ± SD). We calculated β for three frequency ranges: 1) 0.083–1; 2) 1–6; and 3) 6–60 cycles/h. The β for all three regions differed ( P < 0.01). For the two higher frequency ranges, β indicated a fractal relationship (β6–60/h = 1.27 ± 0.01; β1–6/h = 1.80 ± 0.16). Conversely, the slope of the lowest frequency region (i.e., the shoulder) was nearly flat (β0.083–1 /h = 0.32 ± 0.28). We simulated the BP time series as a random walk about 100 mmHg with ranges above and below of 10, 30, and 50 mmHg and with Δ from 0.5 to 2.5. The spectrum for the conditions mimicking actual BP time series (i.e., range, 85–115 mmHg; Δ, 2.00) resembled the observed spectra, with β in the lowest frequency range = 0.207 and fractal-like behavior in the two higher frequency ranges (β = 1.707 and 2.057). We suggest that the combined actions of mechanisms limiting the excursion of arterial BP produce the shoulder in the spectrum and that Δ contributes to determining β.
Effects of Type II diabetes on capillary hemodynamics in skeletal muscle
Authors: Padilla Danielle J. , McDonough Paul , Behnke Brad J. , Kano Yutaka , Hageman K. Sue , Musch Timothy I. , Poole David C.
Published: July 2006

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dcwas not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2delivery and diffusive O2transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2exchange characteristic of Type II diabetic patients.
Role of AMP-activated protein kinase in healthy and diseased hearts
Authors: Dolinsky Vernon W. , Dyck Jason R. B.
Published: July 2006

The heart is capable of utilizing a variety of substrates to produce the necessary ATP for cardiac function. AMP-activated protein kinase (AMPK) has emerged as a key regulator of cellular energy homeostasis and coordinates multiple catabolic and anabolic pathways in the heart. During times of acute metabolic stresses, cardiac AMPK activation seems to be primarily involved in increasing energy-generating pathways to maintain or restore intracellular ATP levels. In acute situations such as mild ischemia or short durations of severe ischemia, activation of cardiac AMPK appears to be necessary for cardiac myocyte function and survival by stimulating ATP generation via increased glycolysis and accelerated fatty acid oxidation. Whereas AMPK activation may be essential for adaptation of cardiac energy metabolism to acute and/or minor metabolic stresses, it is unknown whether AMPK activation becomes maladaptive in certain chronic disease states and/or extreme energetic stresses. However, alterations in cardiac AMPK activity are associated with a number of cardiovascular-related diseases such as pathological cardiac hypertrophy, myocardial ischemia, glycogen storage cardiomyopathy, and Wolff-Parkinson-White syndrome, suggesting the possibility of a maladaptive role. Although the precise role AMPK plays in the diseased heart is still in question, it is clear that AMPK is a major regulator of cardiac energy metabolism. The consequences of alterations in AMPK activity and subsequent cardiac energy metabolism in the healthy and the diseased heart will be discussed.
ENaC proteins contribute to VSMC migration
Authors: Grifoni Samira C. , Gannon Kimberly P. , Stec David E. , Drummond Heather A.
Published: July 2006

Vascular smooth muscle cell (VSMC) migration plays a key role in tissue repair after arterial wall injury. VSMC migration requires integration of chemical and mechanical signaling mechanisms. Recently, we showed that epithelial Na+channel (ENaC) proteins are expressed in VSMCs and that ENaC inhibition abolishes pressure-induced constriction in isolated artery segments. However, whether ENaC proteins play a role in VSMC migration is unknown. The goal of this study was to determine whether ENaC molecules are required for VSMC migration. Using RT-PCR, immunoblotting, and immunolabeling, we detected expression of α-, β-, and γENaC transcripts and proteins in cultured VSMCs (SV40-LT and A10 cells). Of the three proteins, βENaC was the most readily detected in both cell lines by immunolocalization and Western blotting. Inhibition of ENaC activity with 1 μM benzamil blunted VSMC migration associated with wound healing (40.3% at 8 h and 26.2% at 24 h) and in response to the chemotactic stimulant platelet-derived growth factor-BB (38.1%). Furthermore, silencing ENaC gene expression with small interfering RNA blunted VSMC migration. These data indicate that expression of ENaC proteins is required for normal VSMC migration and suggest a potential new role for ENaC proteins in vascular tissue repair.
Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure
Authors: Greer James J. M. , Kakkar Aman K. , Elrod John W. , Watson Lewis J. , Jones Steven P. , Lefer David J.
Published: July 2006

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase endothelial nitric oxide synthase (eNOS) activity by multiple mechanisms. We previously reported that genetic overexpression of eNOS improves survival and cardiac function in congestive heart failure (CHF). In the present study, we tested the hypothesis that low-dose treatment with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor exerts beneficial effects on survival and/or cardiac function in a murine model of CHF. Mice were subjected to permanent ligation of the left coronary artery and randomized to receive either saline vehicle or simvastatin (0.25 mg/kg) 2 h after myocardial infarction and daily (0.25 mg/kg) for 7 days, followed by 21 days of administration every other day for a total duration of 28 days. Myocardial infarct size was not reduced by simvastatin therapy ( P = not significant between groups). Simvastatin treatment did significantly ( P < 0.05) improve survival (45%) compared with vehicle treatment (25%). In addition, simvastatin treatment significantly improved ( P < 0.01) left ventricular function and significantly ( P < 0.01) abrogated cardiac hypertrophy and pulmonary edema compared with vehicle treatment. The protective effects of simvastatin were abrogated by delayed initiation of treatment or genetic ablation of eNOS. In conclusion, low-dose simvastatin therapy significantly improves survival and cardiac function and reduces both cardiac hypertrophy and pulmonary edema via an eNOS-dependent mechanism in a murine model of CHF.
Novel model of inflammatory neointima formation reveals a potential role of myeloperoxidase in neointimal hyperplasia
Authors: Yang Jian , Cheng Yunhui , Ji Ruirui , Zhang Chunxiang
Published: July 2006

Atherosclerosis, which is characterized by neointima formation, is an inflammatory disease. However, there is no inflammatory product-elicited neointimal model to support the causal role of inflammation in atherogenesis. We reported previously that leukocyte-derived MPO induces vascular injury responses such as endothelial dysfunction. We now test the role of MPO in inflammatory neointima formation. We infused temporarily isolated rat common carotid arteries with MPO (200 nM) and incubated for 1 h. We found that although MPO itself did not induce any neointima formation 2 wk after treatment, in the presence of its substrate, hydrogen peroxide, MPO was able to elicit neointimal hyperplasia. We further confirmed that MPO-induced neointimal hyperplasia is mediated by its product, hypochlorous acid (HOCl). HOCl elicited apoptosis both in intima and media followed by vascular proliferative response and resulted in neointima formation with a heterogeneous cell population. Both histological and functional features of HOCl-treated vessels are similar to those in atherosclerotic lesions. To our knowledge, this is the first direct in vivo demonstration of neointimal formation induced by a product of the inflammatory cascade. The results suggest that MPO may be a mediator for pathological neointima growth. This novel neointimal model could be useful for studying inflammation and atherosclerosis.
Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart
Authors: Matsushima Shouji , Kinugawa Shintaro , Ide Tomomi , Matsusaka Hidenori , Inoue Naoki , Ohta Yukihiro , Yokota Takashi , Sunagawa Kenji , Tsutsui Hiroyuki
Published: July 2006

Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme that removes H2O2in both the cytosol and mitochondia. We hypothesized that the overexpression of GSHPx gene could attenuate left ventricular (LV) remodeling in diabetes mellitus (DM). We induced DM by injection of streptozotocin (160 mg/kg ip) in male GSHPx transgenic mice (TG+DM) and nontransgenic wildtype littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared with WT mice, with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 wk were significantly lower than those in WT+DM (58 ± 3 vs. 71 ± 5 nmol/g, P < 0.05). Heart rate and aortic blood pressure were comparable between groups. Systolic function was preserved normal in WT+DM and TG+DM mice. In contrast, diastolic function was impaired in WT+DM and was improved in TG+DM as assessed by the deceleration time of peak velocity of transmitral diastolic flow and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 13.5 ± 1.2 vs. 8.9 ± 0.7 ms, P < 0.01). The TG+DM values were comparable with those of WT+Control (tau; 7.8 ± 0.2 ms). Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis, and apoptosis. Overexpression of GSHPx gene ameliorated LV remodeling and diastolic dysfunction in DM. Therapies designed to interfere with oxidative stress might be beneficial to prevent cardiac abnormalities in DM.