bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of a Ubiquitin-like Protein Paz2 Conducted Micropexophagy through Formation of a Novel Membrane Structure
Authors: Mukaiyama Hiroyuki , Baba Misuzu , Osumi Masako , Aoyagi Satoshi , Kato Nobuo , Ohsumi Yoshinori , Sakai Yasuyoshi
Published: September 2003

Microautophagy is a versatile process in which vacuolar or lysosomal membranes directly sequester cytosolic targets for degradation. Recent genetic evidence suggested that microautophagy uses molecular machineries essential for macroautophagy, but the details of this process are still unknown. In this study, a ubiquitin-like protein Paz2 essential for micropexophagy in the yeast Pichia pastoris has been shown to receive modification through the function of Paz8 and Gsa7, yielding a modified form Paz2-I, similar to the ubiquitin-like lipidation of Aut7 that is essential for macroautophagy in Saccharomyces cerevisiae. We identified a novel membrane structure formed after the onset of micropexophagy, which we suggest is necessary for the sequestration of peroxisomes by the vacuole. Assembly of this newly formed membrane structure, which is followed by localization of Paz2 to it, was found to require a properly functioning Paz2-modification system. We herein show that Paz2 and its modification system conduct micropexophagy through formation of the membrane structure, which explains the convergence between micropexophagy and macroautophagy with regard to de novo membrane formation.
Identification of Novel Recognition Motifs and Regulatory Targets for the Yeast Actin-regulating Kinase Prk1p
Authors: Huang Bo , Zeng Guisheng , Ng Alvin Y.J. , Cai Mingjie
Published: September 2003

Prk1p is a serine/threonine kinase involved in the regulation of the actin cytoskeleton organization in the yeast Saccharomyces cerevisiae. Previously, we have identified LxxQxTG as the phosphorylation site of Prk1p. In this report, the recognition sequence for Prk1p is investigated more thoroughly. It is found that the presence of a hydrophobic residue at the position of P-5 is necessary for Prk1p phosphorylation and L, I, V, and M are all able to confer the phosphorylation at various efficiencies. The residue flexibility at P-2 has also been identified to include Q, N, T, and S. A homology-based three-dimensional model of the kinase domain of Prk1p provided some structural interpretations for these substrate specificities. The characterization of the [L/I/V/M]xx[Q/N/T/S]xTG motif led to the identification of a spectrum of potential targets for Prk1p from yeast genome. One of them, Scd5p, which contains three LxxTxTG motifs and is previously known to be important for endocytosis and actin organization, has been chosen to demonstrate its relationship with Prk1p. Phosphorylation of Scd5p by Prk1p at the three LxxTxTG motifs could be detected in vitro and in vivo, and deletion of PRK1 suppressed the defects in actin cytoskeleton and endocytosis in one of the scd5 mutants. These results allowed us to conclude that Scd5p is likely another regulatory target of Prk1p.
Food retail positioning strategy: a means‐end chain analysis
Authors: Devlin Derek , Birtwistle Grete , Macedo Norma
Published: September 2003

This research conducts a means‐end chain analysis of the food sector and explores the extent to which the findings made can be used to inform the retail positioning strategy of food retailers. Using means‐end theory as the theoretical underpinning of the study, the paper employs laddering methodology to identify the linkages between food retail store attributes and personal values. The findings of the paper present a more personally relevant representation of consumer’s perceptual orientations towards food retail store image. At the attribute level “good quality products”; “good reputation”; “store has additional services” and “value for money” are most sought after. These were linked to the consequences “feel good” and to “save time”. Overall, the findings support previous value driven research, concluding that “happiness” and “quality of life” are the most strived for personal values. Strategic implications for retailers are discussed and future research recommendations are made.
The importance of people skills for project managers
Authors: Cowie George
Published: September 2003

This article demonstrates how project managers can achieve greater success if trained in people skills. Project management is an important skill for businesses to have – particularly companies whose business rests on delivering projects. Often project managers are trained in the technical aspects of project management such as setting objectives; critical path analysis; work breakdown structures; resource allocation and risk management. However, the success of a project often rests on the understanding of related people and management issues, rather than technical issues. ITNET, a UK‐based consulting and business process outsourcing company, reveals how adding soft skills training, such as influencing, motivation, and delegation, to technical project management training can positively impact a business.
Abstracting/abstract adaptation to digital environments: research trends
Authors: Pinto Maria
Published: September 2003

The technological revolution is affecting the structure, form and content of documents, reducing the effectiveness of traditional abstracts that, to some extent, are inadequate to the new documentary conditions. Aims to show the directions in which abstracting/abstracts can evolve to achieve the necessary adequacy in the new digital environments. Three researching trends are proposed: theoretical, methodological and pragmatic. Theoretically, there are some needs for expanding the document concept, reengineering abstracting and designing interdisciplinary models. Methodologically, the trend is toward the structuring, automating and qualifying of the abstracts. Pragmatically, abstracts networking, combined with alternative and complementary models, open a new and promising horizon. Automating, structuring and qualifying abstracting/abstract offer some short‐term prospects for progress. Concludes that reengineering, networking and visualising would be middle‐term fruitful areas of research toward the full adequacy of abstracting in the new electronic age.
Interlending and document supply: a review of recent literature – XLVI
Authors: McGrath Mike
Published: September 2003

The consequences of electronic publishing continue to manifest themselves in the 110 journals scanned for this literature review. Pricing, access, e‐books and e‐journals are amongst the issues considered in this issue’s literature review. Further criticism of the publishing sector is identified and the potential for micro payments.
Simulation of viscous 2D‐planar cylindrical geometry deformation using DR‐BEM
Authors: Hernandez J.P. , Osswald T.A. , Weiss D.A.
Published: September 2003

In this paper, a novel boundary element formulation for the deformation of a viscous 2D‐planar cylindrical geometry, immersed in a different viscous fluid and moving towards a rigid wall, is proposed for moderate Reynolds number, considering surface tension effects. The boundary integral formulation for Stokes flow inside and outside the geometry is represented in terms of a combined distribution of a single‐layer and a double‐layer potential of Green functions over the geometry surface. Additionally, non‐linear terms describing effects absent in pure Stokes flow, such as the time derivative of the velocity and inertia, are included. These effects lead to the appearance of domain integrals. Traditional dual reciprocity is applied in order to approximate these domain integrals by a series of particular solutions which are then transformed into boundary integrals. Augmented thin‐plate splines, i.e. r2log(r), plus three additional linear terms from a Pascal triangle expansion were chosen for the dual reciprocity approximation. In order to avoid the discretization of the rigid wall, and using the fact that the velocity on the wall must vanish due to the no‐slip condition, the fundamental solution was modified with a combination of image singularities including an image Stokeslet, a potential dipole and a Stokes‐doublet.
Natural convection flows in complex cavities by BEM
Authors: Škerget L. , Hriberšek M. , Žunič Z.
Published: September 2003

A numerical method for the solution of the Navier‐Stokes equations is developed using an integral representation of the conservation equations. The velocity‐vorticity formulation is employed, where the kinematics is given with the Poisson equation for a velocity vector, while the kinetics is represented with the vorticity transport equation. The corresponding boundary‐domain integral equations are presented along with discussions of the kinetics and kinematics of the fluid flow problem. The boundary‐domain integral formulation is developed and tested for natural convection flows in closed cavities with complex geometries.
A vision of the Internet in 2010
Authors: Reynolds Paul
Published: September 2003

This paper presents a vision of the Internet eight years from now (i.e. in the year 2010). The study underpinning this vision was performed in two steps: the definition of requirements and drivers together with an extrapolation of technology developments. The vision is a direct result of the author’s extensive experience with working with the development of the Internet including his technical leadership of the Mobile Wireless Internet Forum and as a contributor to the Internet Engineering Task Force.
Information portals: casting a new light on learning for universities
Authors: Murray Robin
Published: September 2003

Underpinning growth of the higher education sector is an efficient, modern library service. If the academic library profession is to avoid becoming sidelined by Google‐type search engines and commercial database services, then they must offer a Web presence that delivers relevant, quality approved and personalised access to resources and library services – irrespective of format and location. Many institutions are investigating information portals to secure the library’s technological future. Why? Because information portals can integrate library‐quality resources in any format – physical or digital – and allow them to be searched, located and delivered speedily and efficiently. Information portals can also offer a seamless channel to a choice of content delivery options including OpenURL citation linking, electronic and physical document delivery.
The effects of audio and video correlation and lip synchronization
Authors: Mued L. , Lines B. , Furnell S. , Reynolds P.
Published: September 2003

This paper investigates the interaction effect of audio and video, and studies lip synchronization (lip sync). The study shows a comprehensive evaluation of achievable audio and video quality undertaken based upon different sets of impairments between audio and video, prior to transmission. The tests have been conducted on two different task scenarios, i.e. passive communication and interactive communication (person to person). The research concentrates on quantifying the effects of network impairments (packet loss) on perceived audio and video quality, as well as finding the correlations between audio and video in multimedia applications. The results presented in this paper show the strong interaction dependency between audio and video. It was justified that video has a unique benefit on multimedia quality for its psychological effects. The findings also concluded that the sensory interactions, and the attention given to a particular aspect of performance, are clearly content‐dependent.
Higher education – IT as a catalyst for change
Authors: O’Donoghue John , Singh Gurmak , Handy Darren
Published: September 2003

This paper is based on a review of current literature and addresses issues relating to communication and information technology (C&IT) provision in UK higher educational institutions from a number of perspectives. Suggests that potentially technology can improve the learning environment, but may not yet be the best medium for all situations.
The impact of product category on customer dissatisfaction in cyberspace
Authors: Cho Yooncheong , Im Il , Fjermestad Jerry , Roxanne Hiltz Starr
Published: September 2003

How do online customers judge a product's attributes in cyberspace? Previous studies of online product category suggest that all goods are not equal on the Web, because products have different attributes. Furthermore, the literature assumes that the customer's ability to evaluate product quality on the Web differs according to product attributes. Based on these considerations, the purpose of this study is to determine whether a customer's dissatisfaction and propensity to complain on the Web differ depending on product category. This study examines how selected variables (i.e. monetary, and non‐monetary effort, and the degree of involvement) influenced the impact of product category on customer dissatisfaction. The analysis was performed using survey data, collected both online and offline. The findings suggest the most appropriate strategies online companies should employ for each product category in question.
Trust and control – a symbiotic relationship?
Authors: Skinner Denise , Spira Laura F.
Published: September 2003

Traditional approaches to management which incorporate top‐down systems of control do not readily accommodate the need, imposed by a changing business environment, for more flexible methods of harnessing the knowledge and commitment of employees. In this situation, trust has been recognized as an important factor for organizational success but any relaxation of control may be constrained by the demands of accountability to internal and external stakeholders. In this paper, we illustrate the complexity of the relationship between trust and control in the context of corporate governance by examining the internal audit technique of control self‐assessment. We argue that the dependence of control processes on trust has been insufficiently explored and that neglecting to consider the reciprocal nature of trust relationships from an employee perspective may hamper the effectiveness of control systems designed to enhance accountability.
Faster New Product Development
Authors: Rosenau Milton D.
Published: September 2003

Clearly today's business climate mandates the need for faster development of new products. Drawing upon his experience, Milton Rosenau describes several techniques that have not been mentioned explicitly in recent articles: short, focused development phases; management involvement and support; procurement and use of productivity improvements; multifunctional teamwork; distraction reduction; frozen specifications; and microcomputer‐based project management software.
Organizing for Product Development Projects
Authors: Larson Erik W. , Gobeli David H.
Published: September 2003

How should companies organize to support the development of new products? Erik Larson and David Gobeli assessed the relative effectiveness of five different project management structures by comparing the performance of 540 development projects in terms of cost, schedule and technical performance. The findings contradict Peters and Waterman's popular conclusion that project teams are superior to matrix structures for developing new products and services. Both the balanced matrix and project matrix compared favorably with project teams in terms of cost, schedule and technical performance. Furthermore, the project matrix received a stronger recommendation from managers than the project team. Little support was found for either the functional or functional matrix approach to project management.
An Integrative Model of the New Product Development Process
Authors: Calantone Roger J. , di Benedetto C. Anthony
Published: September 2003

Previous studies of new product development have identified a series of variables that are important determinants of new product success. The goal of this article is to demonstrate the nature of the complex interrelationships that exist among these variables. Roger Calantone and Anthony di Benedetto propose an integrative model of the new product decision process. They examine data gathered from a sample of industrial manufacturing companies and test their model empirically using three‐stage least squares analysis. The article concludes with a discussion of implications for new product managers.
FROM EXPERIENCE The Customer's Eye View of Innovation
Authors: Potter Donald V.
Published: September 2003

Currently, “working close to the market” is in vogue. Yet often we ignore the single most important premise of this basic operating philosophy. Donald Potter reminds us that it is essential that our new product development efforts key on the basic principle of lowering our customers' costs. He describes one way to achieve this objective while referencing his study of over 500 corporate strategies. Too often, marketing research investigates customers' reactions to existing products, not future needs. A better approach is to develop a deep understanding of the customers' economics of using a product over its entire lifetime.
The Effect of Product Design Activities on Commercial Success Levels of New Industrial Products
Authors: Hise Richard T. , O'Neal Larry , McNeal James U. , Parasuraman A.
Published: September 2003

Previous research has investigated the link between product success and key steps in the new products development process. Because the design/development phase of this process uses large proportions of resources, it has been carefully scrutinized. Nevertheless, the impact on new product success levels of an important aspect of this phase—the technically oriented design steps—has not been comprehensively examined and has been neglected in favor of such nontechnical dimensions as the marketing/R&D interface problem. Richard Hise, Larry O'Neal, James McNeal and A. Parasuraman report the results of a study of 195 new industrial products. They conclude that new product developers may jeopardize the success potentials of new industrial products by not performing specific design steps and by instituting an incomplete design/development agenda.
Boundary Role Spanning Behavior, Conflicts and Performance of Industrial Product Managers
Authors: Lysonski Steven , Woodside Arch G.
Published: September 2003

While researchers have probed predictors of product managers' performance in consumer goods firms, few have looked at the performance of the industrial product manager. In this article, Steven Lysonski and Arch Woodside use path analysis to examine causal models of industrial product managers' performance during periods of rapid technological change. Key variables are analyzed, including the effects of environmental uncertainty, boundary spanning behavior, role pressures, role outcomes and two performance measures. A total of 69 industrial product managers from New Zealand Telecom completed a questionnaire that included both operational measures of the key variables and their overall job performance. The results suggest that most of the hypothesized relationships are supportable empirically. Performance was hindered by environmental uncertainty, role conflict, role ambiguity, tension and dissatisfaction. The authors discuss their study's implications for improving the effectiveness of product management practices.
Testing Market Segment Acceptance of New Designs of Industrial Services
Authors: Woodside Arch G. , Pearce William G.
Published: September 2003

This article investigates the designing of a new furnace tube cleaning service to compete successfully against two existing competitors. Arch Woodside and William Pearce report the results of a marketing experiment in which data were obtained from a total of 33 plant engineers and maintenance managers in chemical plants and oil refineries. These respondents assigned shares of requirements to competing services. In all, nine different service problem scenarios were solved by each subject. The marketers of the new service, following the study's recommendations, decided to create four specific, segment‐based marketing strategies. Following implementation, the company's position improved modestly during the next six months in three of the four market segments.
Maxi‐Niching the Way to a Strong Brand: Positioning According to Systemic Dynamics
Authors: Keely Ann
Published: September 2003

Given today's strong emphasis on segmentation and niche marketing, we often overlook the value of broad approaches to our served markets. Ann Keely feels that the buying process can sometimes create a number of opportunities for customers to consider purchasing a brand. In this article, she describes the concept of maxi‐niching and shows how it can increase the odds that customers will select a particular brand. In its broadest sense, the process of maxi‐niching involves developing perfect products. More realistically, it focuses on maximizing the number and diversity of strengths in the brand's profile. Thus, the brand occupies a varied collection of preference niches, increasing its odds of selection and tipping chance to its advantage.
Schedule Emphasis of New Product Development Personnel
Authors: Rosenau Milton D.
Published: September 2003

The emphasis personnel place on the development schedule is one factor in determining how quickly a new product will reach the market. Normally, each team member will stress different development program aspects in ways that depend on their own background, functional specialty and sense of what their management desires. In this article, Milton Rosenau describes a means to measure the emphasis an individual places on schedule and other program aspects. The results of such a measure can then be used to improve team congruity.
Success Factors Of High‐Tech SBUs: Towards a Conceptual Model Based on the Israeli Electronics and Computers Industry
Authors: Dvir Dov , Shenhar Aaron
Published: September 2003

Of the few studies that have been performed on success and failure of business units in industrial organizations, most were based on marketing and financial data collected in the PIMS program. This study explores the factors contributing to success and failure of high‐tech business units. It is based on a survey conducted in the electronics and computers industry in Israel. The article argues that the success of business units in this industry should not be measured in financial terms only. There are two additional dimensions to success: positioning in the market and preparing the necessary assets and infrastructure for future development, manufacturing and marketing of new products.Some unique success and failure factors, other than those revealed in studies at the product level, were found to contribute to the success of high‐tech business units.
Low Frequency Stimulation of Mouse Adrenal Slices Reveals a Clathrin‐Independent, Protein Kinase C‐Mediated Endocytic Mechanism
Authors: Chan Shyue‐An , Smith Corey
Published: September 2003

Evidence suggests that chromaffin cells employ separate mechanisms for evoked endocytosis and granule recycling when stimulated at basal (∼0.5 Hz) and stress‐activated (∼15 Hz) rates. Previous studies have focused mainly on elucidating the cellular mechanisms responsible for membrane recycling under conditions similar to the stress‐activated state and indicate a clathrin/dephosphin‐mediated retrieval via coated pits. However, the mechanism for membrane internalisation at basal stimulus intensity remains largely unexplored. We electrically stimulated chromaffin cells in adrenal tissue slices at the sympathetic basal firing rate and measured cell capacitance in the perforated voltage clamp configuration. A new method for the separation of non‐secretory from secretory cell capacitance signals is presented. Simultaneous catecholamine release was measured electrochemically to isolate the exocytic from endocytic components of the capacitance responses. Using this approach we demonstrate that firing patterns that mimic basal sympathetic input results in rapid and graded membrane retrieval. We show that block of the calcium‐mediated protein phosphatase 2B, a common step in clathrin‐mediated processes, did not alter endocytosis elicited at basal firing levels. We further blocked clathrin‐mediated retrieval with a clathrin/dephosphin‐disrupting peptide (PP‐19) and found endocytosis to be blocked at 15 Hz stimulation but complete and indistinguishable from control cells at 0.5 Hz stimulation. Lastly, pharmacological treatments show that conventional isoforms of protein kinase C (cPKC) are required for the 0.5 Hz‐evoked retrieval mechanism. From these data we conclude that unlike endocytosis evoked under stress conditions, basal firing activity results in a clathrin‐independent rapid membrane retrieval mediated through conventional isoforms of PKC.
F344 Rat
Authors: Holmes Donna J.
Published: September 2003

This document contains a summary of the biological characteristics of the F344 rat. This strain, including calorically restricted individuals, is available from the National Institute on Aging.
SH2 and PTB Domains in Tyrosine Kinase Signaling
Authors: Schlessinger Joseph , Lemmon Mark A.
Published: September 2003

Intracellular signaling pathways that involve protein tyrosine kinases (PTKs) are critical for the control of most cellular processes. Dysfunctions in PTKs, or in the signaling pathways that they regulate, result in a variety of diseases such as cancer, diabetes, immune deficiency, and many others. SH2 (Src homology region 2) and PTB (phosphotyrosine-binding) domains are small protein modules that mediate protein-protein interactions involved in many signal transduction pathways. Both domains were initially identified as modules that recognize phosphorylated tyrosines in receptor tyrosine kinases and other signaling proteins. Subsequent studies have shown that, while binding of SH2 domains to their target proteins is strictly regulated by tyrosine phosphorylation, most PTB domains actually bind to their (nonphosphorylated) targets constitutively. The functions of SH2 and PTB domains include targeting of their host proteins to different cellular compartments, assembly of key components of signaling pathways in response to extracellular signals, and the control of autoinhibition, activation and dimerization of their host proteins. The information flow from the cell surface to different cellular compartments to regulate the cell cycle, cell shape and movement, cell proliferation, differentiation and cell survival are all controlled in part by SH2 and PTB domains that can recognize phosphotyrosine or particular amino acid sequence motifs in a wide variety of target molecules.
Evidence Mounts for Receptor-Independent Activation of Heterotrimeric G Proteins Normally in Vivo: Positioning of the Mitotic Spindle in
C. Elegans
Authors: Manning David R.
Published: September 2003

Examples of the activation of heterotrimeric G proteins in vivo by any means other than through activated cell surface receptors have been limited to pathophysiological phenomena. With the discovery of proteins apart from receptors that facilitate guanine nucleotide exchange and affect G protein subunit dissociation directly, however, the notion of receptor-independent modes of activation in normal circumstances has become a subject of great interest. Three recent publications, each focusing on G protein regulators (GPRs) in asymmetric positioning of the mitotic spindle in the early
Caenorhabditis elegans
embryo, provide substantial support for the likelihood of such a form of activation. The
C. elegans
proteins GPR-1 and GPR-2 each contain a G protein regulatory motif, which supports interaction with Gα
i
-like subunits. Inactivation of the genes encoding GPR-1 and GPR-2 prevents the correct positioning of the mitotic spindle in the one- and two-cell embryo. This phenotype is identical to that achieved by inactivation of genes encoding the Gα subunits GOA-1 and GPA-16. Because signaling in the one- and two-cell embryos is "intrinsic," the data suggest a GPR-dependent, receptor-independent mode of G protein activation. The GPRs interact preferentially with the guanosine diphosphate (GDP)-bound form of Gα subunits, and the GPR motif per se exhibits GDP dissociation inhibitor activity. The actions of the GPRs imply that GDP•Gα•GPR is a key intermediate or effector in force generation relevant to mitotic spindle positioning.
The STAT3 Pathway
Authors: Aaronson David S. , Horvath Curt M.
Published: September 2003

Signal transducer and activator of transcription 3 (STAT3) is widely expressed and activated by various growth-regulating signals, as well as diverse cytokines, that activate gp130 signaling receptors. Hence, STAT3 is critical for embryonic development and stem cell biology, as well as inflammation, growth regulation, and multiple immune regulatory and homeostatic functions. STAT3 is also found in its activated state in a large number of human cancers and has been correlated with oncogenic activity and tumor maintenance in several systems. The Connections Map highlights activation of STAT3 by interleukin 6 and shows that STAT3 serves as an integration point for components in multiple signaling pathways in addition to those involving JAKs, for example, the small guanosine triphosphatase Ras, heterotrimeric guanine nucleotide-binding protein (G proteins) of the G
i/o
family, and the nonreceptor tyrosine kinases of the Src family.

Science Viewpoint

D. S. Aaronson, C. M. Horvath, A road map for those who don't know JAK-STAT.
Science
296
, 1653-1655 (2002). [
Abstract
] [
Full Text
]
Mutation Rate and Evolution of Fluoroquinolone Resistance in
Escherichia coli
Isolates from Patients with Urinary Tract Infections
Authors: Komp Lindgren Patricia , Karlsson Åsa , Hughes Diarmaid
Published: September 2003

Escherichia coli
strains from patients with uncomplicated urinary tract infections were examined by DNA sequencing for fluoroquinolone resistance-associated mutations in six genes:
gyrA
,
gyrB
,
parC
,
parE
,
marOR
, and
acrR
. The 54 strains analyzed had a susceptibility range distributed across 15 dilutions of the fluoroquinolone MICs. There was a correlation between the fluoroquinolone MIC and the number of resistance mutations that a strain carried, with resistant strains having mutations in two to five of these genes. Most resistant strains carried two mutations in
gyrA
and one mutation in
parC
. In addition, many resistant strains had mutations in
parE
,
marOR
, and/or
acrR
. No (resistance) mutation was found in
gyrB
. Thus, the evolution of fluoroquinolone resistance involves the accumulation of multiple mutations in several genes. The spontaneous mutation rate in these clinical strains varied by 2 orders of magnitude. A high mutation rate correlated strongly with a clinical resistance phenotype. This correlation suggests that an increased general mutation rate may play a significant role in the development of high-level resistance to fluoroquinolones by increasing the rate of accumulation of rare new mutations.
Essential Oils as Components of a Diet-Based Approach to Management of
Helicobacter
Infection
Authors: Bergonzelli G. E. , Donnicola D. , Porta N. , Corthésy-Theulaz I. E.
Published: September 2003

An increased density of
Helicobacter pylori
in the gastric mucosa can be associated with more severe gastritis and an increased incidence of peptic ulcers. Therefore, people with asymptomatic gastritis would certainly benefit from a nutritional approach to help them manage the infection and therefore decrease the risk of development of associated pathologies. We analyzed the activities of 60 essential oils against
H. pylori
P1 and identified 30 oils that affected growth, with in vitro inhibition zones ranging between 0.7 and 6.3 cm in diameter. We further analyzed the effects of 16 oils with different activities on
H. pylori
P1 viability. Fifteen showed strong bactericidal activities, with minimal bactericidal concentrations after 24 h ranging from 0.02 to 0.1 g/liter at pH 7.4. Even though slight variations in activities were observed, the essential oils that displayed the strongest bactericidal potentials against
H. pylori
P1 were also active against other
Helicobacter
strains tested. Among the pure constituents of different essential oils tested, carvacrol, isoeugenol, nerol, citral, and sabinene exhibited the strongest anti-
H. pylori
activities. Although oral treatment of
H. pylori
SS1-infected mice with carrot seed oil did not result in significant decreases in the bacterial loads in the treated animals compared to those in the control animals, in all experiments performed, the infection was cleared in 20 to 30% of carrot seed oil-treated animals. Our results indicate that essential oils are unlikely to be efficient anti-
Helicobacter
agents in vivo. However, their effects may not be irrelevant if one plans to use them as food additives to complement present therapies.
In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone
Authors: Nilius Angela M. , Shen Linus L. , Hensey-Rudloff Dena , Almer Laurel S. , Beyer Jill M. , Balli Darlene J. , Cai Yingna , Flamm Robert K.
Published: September 2003

ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family
Enterobacteriaceae
, although it was less active than the comparators against
Citrobacter freundii
and
Serratia marcescens.
The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including
Haemophilus influenzae
,
Moraxella catarrhalis
,
Neisseria gonorrhoeae
, and
Legionella
spp. and against
Pseudomonas aeruginosa
and
Helicobacter pylori
. ABT-492 was as active as trovafloxacin against
Chlamydia trachomatis
, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant
Streptococcus pneumoniae
, including strains resistant to penicillin and macrolides, and
H. influenzae
, including β-lactam-resistant strains. It retained greater in vitro activity than the comparators against
S. pneumoniae
and
H. influenzae
strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either
Staphylococcus aureus
or
Escherichia coli
were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections.
Efficacy of Multiple- or Single-Dose Cidofovir against Vaccinia and Cowpox Virus Infections in Mice
Authors: Quenelle Debra C. , Collins Deborah J. , Kern Earl R.
Published: September 2003

Orthopoxviruses, including variola and monkeypox, pose risks to human health through natural transmission or potential bioterrorist activities. Since vaccination has not recently been utilized for control of these infections, there is renewed effort in the development of antiviral agents not only for postexposure smallpox therapy but also for treatment of adverse reactions following vaccination. The objectives of this study were to expand on the results of others that cidofovir (CDV) is effective in mice inoculated with cowpox virus (CV) or vaccinia virus (VV) and to document the efficacy of single and interval dosing beginning prior to or after infection, particularly including evaluations using suboptimal doses of CDV. We utilized BALB/c or SCID mice inoculated with CV or VV as models for systemic poxvirus infections. BALB/c mice were inoculated intranasally with CV or VV and treated with CDV prior to or after virus inoculation. CDV, at concentrations as low as 0.7 to 6.7 mg/kg of body weight/day for 5 days, conferred significant protection when treatment was initiated as late as 72 to 96 h postinfection. A single-dose pretreatment or posttreatment with CDV at 3 to 100 mg/kg was effective when given as early as 5 days prior to infection or as late as 3 days after infection with either VV or CV. Interval treatments given every third day beginning 72 h postinfection using 6.7 or 2 mg of CDV/kg also proved effective against CV infections. When SCID mice were inoculated intraperitoneally with CV or VV and treated for 7 to 30 days with CDV, all the mice eventually died during or after cessation of treatment; however, significant delays in time to death and reduction of virus replication in organs occurred in most treated groups, and no resistance to CDV was detected.
DNA Gyrase and Topoisomerase IV Mutations in Clinical Isolates of
Ureaplasma
spp. and
Mycoplasma hominis
Resistant to Fluoroquinolones
Authors: Bébéar C. M. , Renaudin H. , Charron A. , Clerc M. , Pereyre S. , Bébéar C.
Published: September 2003

Twelve clinical isolates of
Ureaplasma
spp. and one isolate of
Mycoplasma hominis
were examined for resistance to fluoroquinolones. Previously described mutations at positions 83 and 95 in GyrA (
Escherichia coli
numbering) and positions 80 and 87 in ParC were found. Unusual alterations were described at positions ParC 123 and 134.
Erythromycin Esterase Gene
ere
(A) Is Located in a Functional Gene Cassette in an Unusual Class 2 Integron
Authors: Biskri Latefa , Mazel Didier
Published: September 2003

The gene
ere
(A) of the plasmid pIP1100 is larger than originally reported and is organized as an integron gene cassette. The
ere
(A) gene cassette carries its own promoter and is propagated by a class 2 integron with an insertion sequence element, IS
1
, inserted upstream of the
intI2
gene. The mobility of the
ere
(A) cassette has been demonstrated.
Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals
Authors: Buzio L , De Palma G , Mozzoni P , Tondel M , Buzio C , Franchini I , Axelson O , Mutti A
Published: September 2003

Aims:To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1andGSTT1) in renal cell cancer (RCC).

Methods:One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire.

Results:Subjects withGSTM1present genotype showed higher risks for RCC, compared toGSTM1null subjects, if exposed to metals (OR 2.73; 95% CI 0.91 to 8.22v1.14; 95% CI 0.46 to 2.82) or pesticides (OR 3.46; 95% CI 1.12 to 10.74v1.59; 95% CI 0.48 to 5.34). TheGSTT1present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with thoseGSTT1null.

Conclusions:Results support the hypothesis thatGSTM1andGSTT1polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.
Effects of Aspirin Dose When Used Alone or in Combination With Clopidogrel in Patients With Acute Coronary Syndromes
Authors: Peters Ron J.G. , Mehta Shamir R. , Fox Keith A.A. , Zhao Feng , Lewis Basil S. , Kopecky Steven L. , Diaz Rafael , Commerford Patrick J. , Valentin Vicent , Yusuf Salim
Published: September 2003

Background—

We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome (ACS).

Methods and Results—

In the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, 12 562 patients with ACS using aspirin, 75 to 325 mg daily, were randomized to clopidogrel or placebo for up to 1 year. In this analysis, patients were divided into the following 3 aspirin dose groups: ≤100 mg, 101 through 199 mg, and ≥200 mg. The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: ≤100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and ≥200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]). The incidence of major bleeding increased with increasing aspirin dose both in the placebo group (1.9%, 2.8%, and 3.7%, respectively;
P
=0.0001) and the clopidogrel group (3.0%, 3.4%, and 4.9%, respectively;
P
=0.0009); thus, the excess risk with clopidogrel was 1.1%, 1.2%, and 1.2%, respectively. The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 (95% CI 1.29 to 2.72) in the placebo group, 1.6 (95% CI 1.19 to 2.23) in the clopidogrel group, and 1.7 (95% CI 1.36 to 2.20) in the combined group.

Conclusions—

In patients with ACS, adding clopidogrel to aspirin is beneficial regardless of aspirin dose. Bleeding risks increase with increasing aspirin dose, with or without clopidogrel, without any increase in efficacy. Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg, with or without clopidogrel.
Angiotensin-(1-7) Formation in the Intact Human Heart
Authors: Zisman Lawrence S. , Meixell Glenn E. , Bristow Michael R. , Canver Charles C.
Published: September 2003

Background—

Several enzymes that hydrolyze angiotensin I (Ang I) and Ang II to Ang-(1-7) have been identified, but their relative importance in the intact human heart is not known.

Methods and Results—

Intracoronary (IC)
123
I-Ang I was administered to 4 heart transplantation recipients. Arterial and coronary sinus (CS) samples were taken before and after coadministration of IC enalaprilat.
123
I-Ang metabolites were separated by high-pressure liquid chromatography, and
123
I-Ang-(1-7) and
123
I-Ang II were quantified across the myocardial circulation.
123
I-Ang II formation (as measured by fractional conversion) at steady state was 0.43±0.05 and was reduced to 0.042±0.02 after IC enalaprilat (
P
<0.01). The fractional conversion of
123
I-Ang-(1-7) was 0.198±0.032 but was reduced to 0.06±0.01 during IC enalaprilat (
P
<0.01). Net Ang II production at steady state was 2720±704 pg/min. Ang-(1-7) production was 3489±768 pg/min. After IC enalaprilat, Ang II production fell to 436±66.8 pg/min (
P
<0.05 versus Ang II production). After suppression of Ang II production with enalaprilat, there was net uptake of Ang-(1-7): −289±144 pg/min (
P
<0.05).

Conclusions—

Ang-(1-7) was formed in the intact human myocardial circulation and was decreased when Ang II formation was suppressed. These data indicate that the major pathway for Ang-(1-7) generation in the intact human heart was dependent on substrate availability of Ang II. Ang-(1-7)–forming enzymes that demonstrate substrate preference for Ang II are likely to play an important role in the regulation of Ang-(1-7) formation in the intact human heart.
A Ubiquitous Splice Variant and a Common Polymorphism Affect Heterologous Expression of Recombinant Human SCN5A Heart Sodium Channels
Authors: Makielski Jonathan C. , Ye Bin , Valdivia Carmen R. , Pagel Matthew D. , Pu Jielin , Tester David J. , Ackerman Michael J.
Published: September 2003

Amino acid sequence variations in SCN5A are known to affect function of wild-type channels and also those with coexisting mutations; therefore, it is important to know the exact sequence and function of channels most commonly present in human myocardium.
SCN5A
was analyzed in control panels of human alleles, demonstrating that the existing clones (hH1, hH1a, hH1b) each contained a rare variant and thus none represented the common sequence. Confirming prior work, the H558R polymorphism was present in ≈30% of subjects. Quantitative mRNA analysis from human hearts showed that a shorter 2015 amino acid splice variant lacking glutamine at position 1077 (Q1077del) made up 65% of the transcript in every heart examined. Age, sex, race, or structural heart disease did not affect this proportion of Q1077del. Estimated population frequencies for the four common variants were 25% SCN5A, 10% [H558R], 45% [Q1077del], and 20% [H558R;Q1077del], where the reference sequence SCN5A is GenBank AC137587. When expressed in HEK-293 cells, these common variants had a more positive mid-point of the voltage dependence of inactivation than the standard clone hH1. Also, channels containing Q1077 expressed smaller currents. When H558R was present with Q1077 ([H558R]), current expression was profoundly reduced despite normal trafficking to the cell surface. Thus, four variant sequences for SCN5A are commonly present in human myocardium and they exhibit functional differences among themselves and with the previous standard clone. These results have implications for the choice of background sequence for experiments with heterologous expression systems, and possibly implications for electrophysiological function in vivo.
Vegetable and Fruit Intake and Stroke Mortality in the Hiroshima/Nagasaki Life Span Study
Authors: Sauvaget C. , Nagano J. , Allen N. , Kodama K.
Published: September 2003

Background and Purpose—

Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately.

Methods—

A prospective cohort study of 40 349 Japanese men and women was initiated in 1980–1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered.

Results—

A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction.

Conclusions—

Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.