bluuebunny/crossref_metadata_2025 huggingface dataset:
The Grammaticalization of Small Size Nouns
Authors: Brems Lieselotte
Published: November 2007

This article discusses the grammaticalized status of low-frequency small size nouns (henceforth SSNs), such as jot of, scrap of, and flicker of, which cannot have engaged in the spiral routinization processes with attrition, decategorialization, and grammatical reanalysis characteristic of “default” grammaticalization. The proposal to account for the grammatical status of low-frequency complex prepositions in terms of grammaticalization by analogy is partially rejected. Corpus studies on nine SSNs show that mere analogy with one highly schematic construction, a+SSN+ of, as instantiated by frequent a bit of, cannot be the sole factor involved in the grammaticalization of infrequent SSNs. Instead, more complex analogies with different quantifier models are involved which incorporate polarity sensitivity, similar to some and any, and which seem to serve as distant models in these analogies. However, in contrast to some and any, which can be used generally in quantifying contexts, the infrequent SSNs are further characterized by specific collocational and pragmatic values, and their appearance seems restricted to particular discourse contexts. More generally, the present article supports the claim that grammaticalization as such directly works on and results in (at least partially) substantive constructions, rather than schematic ones. It furthermore makes a claim for caution in describing what serves as a source for analogical extension, both in terms of describing all of the factors that come into play and deciding on the specific level of schematicity at which these need to be described.
Beyond 'In so far as' Questions
Authors: Heikkilä Heikki
Published: November 2007

■ Sociological analysts of the European public sphere (EPS) are not great believers in the assumption that an EPS will emerge. The argument stems from cumulative empirical evidence stating that contemporary communication structures and practices do not live up to the ideals of the public sphere; not even in their moderate forms. While this line of analysis is useful, it runs the risk of ignoring the fact that the public sphere is not a fixed, but an emergent concept. In order to safeguard this emergent aspect, it is proposed that we should move forward from `insofar as' questions and start looking for social imaginaries of an EPS in more `unlikely places'. A plausible object for such scrutiny would be the European Union and its information policies. ■
Journalists as Commentatorson European Politics
Authors: Statham Paul
Published: November 2007

■ Questions of media performance seem to be inherently linked to any proposed solutions to Europe's perceived `democratic deficit'. This article addresses a specific part of this story: the attempts by journalists from the national press to commentate politically on European affairs, and their self-perceptions about the opportunities and constraints facing them. The article's main enquiry is whether commentating on Europe is different from commentating on national affairs. A model was constructed to assess types of political advocacy. The empirical study is based on interviews with a sample of journalists with four different roles, and from four different types of newspaper, from seven European countries. The main finding is that to the extent that they take on an advocacy role at all with regard to Europe, journalists see themselves as adopting an educational mode of raising public awareness, more than a political `partisan' or `ideological campaign' mode. Such findings are then discussed in relation to the broader issue of media performance over Europe. ■
Distribution of androstenedione and its effects on total free fatty acids in pregnant rats
Authors: Kim C.S. , Ross I.A. , Sprando R.L. , Johnson W.D. , Sahu S.C. , Flynn T.J. , Wiesenfeld P.L. , Collins T.F.X. , O'Neilll R.K. , Sapienza P.
Published: November 2007

Androstenedione, an anabolic steroid used to enhance athletic performance, was administered in corn oil by gastric intubation once daily in the morning to nonpregnant female rats at a dose of 5 or 60mg/kg/day, beginning two weeks before mating and continuing through gestation day (GD) 19. On GD 20, the distribution of androstenedione and other steroid metabolites was investigated in the maternal plasma and target organs, including brain and liver. The concentration of estradiol in plasma approached a statistically significant increase after treatment as compared with the controls, whereas the levels of androstenedione, testosterone and progesterone were not significantly different from the controls. In the liver, the concentrations of androstenedione and estradiol only were increased in a dose-related manner. None of these steroids was detectable in the brain. Androstenedione treatment also produced changes in the level of selected free fatty acids (FFAs) in the maternal blood, brain, liver and fetal brain. The concentrations of palmitic acid (16:0) and stearic acid (18:0) in the plasma were not significantly different between the controls and treated rats. However, oleic acid (18:1), linoleic acid (18:2) and docosahexaenoic acid (DHA, 22:6) were 17.94 ± 2.06 μg/ml, 24.23 ± 2.42 μg/ml and 4.08 ± 0.53 μg/ml, respectively, in the controls, and none of these fatty acids was detectable in the treated plasma. On the other hand, palmitic, stearic, oleic, linoleic and DHA were present in both control and treated livers. Among the FFAs in liver, linoleic and DHA were increased 87% and 169%, respectively, over controls. Palmitic, stearic and oleic acids were not significantly affected by the 60 mg/kg treatment. These were present in both control maternal and fetal brains, whereas linoleic acid was found only in fetal brain control. DHA was present only in the control maternal brain (0.02 ± 0.02 μg/mg protein) and fetal brain (0.24 ± 0.15 μg/mg protein). The results indicated that androstenedione exhibits significantly different effects on the FFA composition among target organs during pregnancy.
Gambling partners? The risky outcomes of workplace partnerships
Authors: Jenkins Jean
Published: November 2007

This article analyses the motivations and dynamics of union—management partnership at two manufacturing plants located in the industrial region of South Wales in the UK. Each plant was a subsidiary of an international parent corporation: one in the aluminium sector and one in autocomponents manufacture. For meaningful partnership to be achieved, it is assumed that both union and management partners engage in reciprocal elements of risk in the hope — or gamble — that mutually beneficial outcomes will be forthcoming. But this article will argue that the causal association between partnership and substantive outcomes is contested. It suggests that analysis of partnership should focus on the context in which it is found, the motivations of key actors, and the nature of reciprocal risk for labour and management, in order to gain optimum insight into modern industrial relations and illuminate the political implications for the collective representation of labour's interests in contemporary capitalist society.
Implications of family-friendly policies for organizational culture: findings from two case studies
Authors: Callan Samantha
Published: November 2007

Formal policies intended to enable employees to meet family commitments may be important indicators of an organization's intent, but they do not guarantee that the informal culture is supportive of employees' families or their attempts to manage occasionally conflicting priorities (Lewis, 1997; Lewis and Lewis, 1996). Two case studies were conducted to identify salient aspects of the culture of two organizations and the extent to which changes in culture result from the implementation of family-friendly policies.The wider issue of the ease with which purposive cultural change or organizational learning may be engendered to ameliorate employees' work—life balance is also considered.
Partners in Diabetes
Authors: Mendenhall Tai J. , Doherty William J.
Published: November 2007

Diabetes is a growing problem that threatens both individual health and health care systems throughout the industrialized world. This study analyzes the process and evolution of a collaborative project dealing with diabetes and employing action research methodology and the Citizen Health Care model. Partners in Diabetes (PID) was created through a democratic process among patients, families and providers in a primary care setting in the United States. Fourteen PID `support partners' were nominated by their physicians to receive training and then reach out to other patients and families across a variety of contexts (e.g. home, clinic, telephone). We conducted qualitative analyses of detailed meeting process-notes spanning more than three years, and key-informant interviews with providers, patients and family members. We identified key developmental themes, including how providers and patients learned to overcome traditional hierarchy, how PID was designed and implemented, what challenges were encountered and what mistakes were made. Lessons for extending similar projects are highlighted.
Multiple chronic diseases and quality of life: patterns emerging from a large national sample, Australia
Authors: Walker Agnes Emilia
Published: November 2007

Objectives: To assess the importance of multiple chronic diseases (co-morbidities) to how people feel about their lives generally. To do this, we studied the associations between co-morbidities and indicators of quality of life and/or psychological distress.

Methods: Analysis of unit record cross-sectional data from Australian national surveys for the population aged 20 years or more. Identification of an appropriate indicator of multiple chronic diseases (i.e. co-morbidities). Use of logistic regression techniques to study associations between: (1) co-morbidities and demographic, socio-economic and risk factor variables; and (2) quality of life (general and psychological distress) and demographic, socio-economic and health status indicators.

Results: Older people, obese persons, women, persons with low socio-economic status and those living alone had significantly greater probability of having three or more chronic illnesses than did other people aged 20+ years (p<0.0001). Also, people with co-morbidities and/or with poor self-rated general health, those living alone, people with low educational qualifications and persons with low socio-economic status were more likely to feel dissatisfied, unhappy or terrible about their lives and to have moderate, high or very high psychological distress scores than the rest of the 20+-year-old population (p<0.0001).

Conclusions: Multiple chronic diseases were found to have a considerable negative impact on quality of life, not only in terms of how people felt about their lives generally, but also in terms of the extent of their psychological distress.
Anxiety and health-related quality of life of patients undergoing total hip arthroplasty for osteoarthritis
Authors: Montin Liisa , Leino-Kilpi Helena , Katajisto Jouko , Lepistö Jyri , Kettunen Jyrki , Suominen Tarja
Published: November 2007

Objective: Osteoarthritis in a hip not only causes pain and decreases physical function, which are the most common reasons for total hip arthroplasty, but also causes anxiety and reduces patients' health-related quality of life (HRQoL). The objective of this study was to evaluate patients' anxiety and its possible relationship with HRQoL before and after surgery.

Methods: In this longitudinal follow-up study, the State Trait Anxiety Inventory was used to measure patients' (n = 100) level of anxiety before surgery and at 1 month, 3 months and 6 months post-operatively. The Sickness Impact Profile was used to measure patients' total HRQoL before surgery and post-operatively at 3 and 6 months.

Results: Before surgery, patients' trait and state anxiety were moderate. Patients' pre-operative trait anxiety impaired HRQoL both before and after surgery. After surgery, state anxiety remained at a moderate level, although a few minor peaks were observed, but no relationship between state anxiety and HRQoL was found.

Discussion: Patients' needs and characteristics should be carefully assessed when planning post-operative care and support. Nurses should be aware of factors that may relate to anxiety and also consider different methods of supporting patients' recovery.
The Russian Furniture Industry: Firms' Upgrading According to the Value-Chain Theory
Authors: Avdasheva Svetlana
Published: November 2007

The Russian furniture market is demonstrating fast and stable growth, which is both attractive and promising. At the same time, most Russian furniture producers exhibit insufficient and inconsistent restructuring. Taking into account the results of in-depth, semi-structured interviews with different types of furniture market participants (furniture producers, including downstream integrated and specialised; retailers; and suppliers of raw materials) the paper describes the restructuring strategies of domestic firms in the framework of the valuechain theory. Particularly, the article aims to explain the obstacles for Russian producers to upgrade as suppliers of specialised products, or parts of products, despite the experience of successful restructuring in the furniture industry of the former socialist countries in East Europe that resulted from a fragmentation of production.
Activation of Epac stimulates integrin-dependent homing of progenitor cells
Authors: Carmona Guillaume , Chavakis Emmanouil , Koehl Ulrike , Zeiher Andreas M. , Dimmeler Stefanie
Published: November 2007

Cell therapy is a novel promising option for treatment of ischemic diseases. Administered endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve neovascularization. However, the number of cells that home to ischemic tissues is restricted. The GTPase Rap1 plays an important role in the regulation of adhesion and chemotaxis. We investigated whether pharmacologic activation of Epac1, a nucleotide exchange protein for Rap1, which is directly activated by cAMP, can improve the adhesive and migratory capacity of distinct progenitor cell populations. Stimulation of Epac by a cAMP-analog increased Rap1 activity and stimulated the adhesion of human EPCs, CD34+ hematopoietic progenitor cells, and mesenchymal stem cells (MSCs). Specifically, short-term stimulation with a specific Epac activator increased the β2-integrin–dependent adhesion of EPCs to endothelial cell monolayers, and of EPC and CD34+ cells to ICAM-1. Furthermore, the Epac activator enhanced the β1-integrin–dependent adhesion of EPCs and MSCs to the matrix protein fibronectin. In addition, Epac1 activation induced the β1- and β2-integrin–dependent migration of EPCs on fibronectin and fibrinogen. Interestingly, activation of Epac rapidly increased lateral mobility of β1- and β2-integrins, thereby inducing integrin polarization, and stimulated β1-integrin affinity, whereas the β2-integrin affinity was not increased. Furthermore, prestimulation of EPCs with the Epac activator increased homing to ischemic muscles and neovascularization-promoting capacity of intravenously injected EPCs in the model of hind limb ischemia. These data demonstrate that activation of Epac1 increases integrin activity and integrin-dependent homing functions of progenitor cells and enhances their in vivo therapeutic potential. These results may provide a platform for the development of novel therapeutic approaches to improve progenitor cell homing.
Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak–like cells and enables isolation of primitive hematopoietic precursors
Authors: Davis Richard P. , Ng Elizabeth S. , Costa Magdaline , Mossman Anna K. , Sourris Koula , Elefanty Andrew G. , Stanley Edouard G.
Published: November 2007

Differentiating human embryonic stem cells (HESCs) represent an experimental platform for establishing the relationships between the earliest lineages that emerge during human development. Here we report the targeted insertion in HESCs of sequences encoding green fluorescent protein (GFP) into the locus of MIXL1, a gene transiently expressed in the primitive streak during embryogenesis.1,2 GFP fluorescence in MIXL1GFP/w HESCs differentiated in the presence of BMP4 reported the expression of MIXL1, permitting the identification of viable human primitive streak-like cells. The use of GFP as a reporter for MIXL1 combined with cell surface staining for platelet-derived growth factor receptor alpha (PDGFRα) enabled the isolation of a cell population that was highly enriched in primitive hematopoietic precursors, the earliest derivatives of the primitive streak. These experiments demonstrate the utility of MIXL1GFP/w HESCs for analyzing the previously inaccessible events surrounding the development of human primitive streak-like cells and their subsequent commitment to hematopoiesis.
Indirect involvement of allergen-captured mast cells in antigen presentation
Authors: Kambayashi Taku , Baranski Jan D. , Baker Rebecca G. , Zou Tao , Allenspach Eric J. , Shoag Jonathan E. , Jones Peter L. , Koretzky Gary A.
Published: November 2007

It is generally thought that mast cells influence T-cell activation nonspecifically through the release of inflammatory mediators. In this report, we provide evidence that mast cells may also affect antigen-specific T-cell responses by internalizing immunoglobulin E–bound antigens for presentation to antigen-specific T cells. Surprisingly, T-cell activation did not require that mast cells express major histocompatibility complex class II, indicating that mast cells were not involved in the direct presentation of the internalized antigens. Rather, the antigen captured by mast cells is presented by other major histocompatibility complex class II+ antigen-presenting cells. To explore how this may occur, we investigated the fate of mast cells stimulated by antigen and found that FcϵRI crosslinking enhances mast cell apoptosis. Cell death by antigen-captured mast cells was required for efficient presentation because protection of mast cell death significantly decreased T-cell activation. These results suggest that mast cells may be involved in antigen presentation by acting as an antigen reservoir after antigen capture through specific immunoglobulin E molecules bound to their FcϵRI. This mechanism may contribute to how mast cells impact the development of T-cell responses.
Enucleation of primitive erythroid cells generates a transient population of “pyrenocytes” in the mammalian fetus
Authors: McGrath Kathleen E. , Kingsley Paul D. , Koniski Anne D. , Porter Rebecca L. , Bushnell Timothy P. , Palis James
Published: November 2007

Enucleation is the hallmark of erythropoiesis in mammals. Previously, we determined that yolk sac–derived primitive erythroblasts mature in the bloodstream and enucleate between embryonic day (E)14.5 and E16.5 of mouse gestation. While definitive erythroblasts enucleate by nuclear extrusion, generating reticulocytes and small, nucleated cells with a thin rim of cytoplasm (“pyrenocytes”), it is unclear by what mechanism primitive erythroblasts enucleate. Immunohistochemical examination of fetal blood revealed primitive pyrenocytes that were confirmed by multispectral imaging flow cytometry to constitute a distinct, transient cell population. The frequency of primitive erythroblasts was higher in the liver than the bloodstream, suggesting that they enucleate in the liver, a possibility supported by their proximity to liver macrophages and the isolation of erythroblast islands containing primitive erythroblasts. Furthermore, primitive erythroblasts can reconstitute erythroblast islands in vitro by attaching to fetal liver–derived macrophages, an association mediated in part by α4 integrin. Late-stage primitive erythroblasts fail to enucleate in vitro unless cocultured with macrophage cells. Our studies indicate that primitive erythroblasts enucleate by nuclear extrusion to generate erythrocytes and pyrenocytes and suggest this occurs in the fetal liver in association with macrophages. Continued studies comparing primitive and definitive erythropoiesis will lead to an improved understanding of terminal erythroid maturation.
Partial reversal of experimental pulmonary hypertension by phosphodiesterase-3/4 inhibition
Authors: Dony E. , Lai Y-J. , Dumitrascu R. , Pullamsetti S. S. , Savai R. , Ghofrani H. A. , Weissmann N. , Schudt C. , Flockerzi D. , Seeger W. , Grimminger F. , Schermuly R. T.
Published: November 2007

Phosphodiesterase (PDE) inhibitors are currently under investigation for the therapy of pulmonary hypertension.

The present study was designed to investigate chronic effects of oral pumafentrine, a mixed selective PDE-3/4 inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension in rats.

Treatment with pumafentrine (10 mg·kg−1daily) from week 4 to 6 after a single injection of MCT (60 mg·kg−1) partially reversed pulmonary hypertension and right heart hypertrophy in rats. In addition, small pulmonary arterial muscularisation, media hypertrophy and decrease in lumen area were largely reversed. Inhibition of smooth muscle proliferation under pumafentrine was demonstratedin vivoas was a pro-apoptotic effect of pumafentrine on vascular cells. Moreover, pumafentrine dose-dependently increased cyclic adenosine monophosphate levels and inhibited proliferation of cultured pulmonary arterial smooth muscle cells.

In conclusion, oral pumafentrine partially reverses monocrotaline-induced pulmonary hypertension, lung vascular remodelling and right heart hypertrophy in rats.
Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation
Authors: Brekke P. H. , Omland T. , Holmedal S. H. , Smith P. , Søyseth V.
Published: November 2007

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated.

From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000–2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT ≥0.04 μg·L−1were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses.

After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15–2.34).

In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.
Neural respiratory drive during apnoeic events in obstructive sleep apnoea
Authors: Luo Y. M. , Wu H. D. , Tang J. , Jolley C. , Steier J. , Moxham J. , Zhong N. S. , Polkey M. I.
Published: November 2007

For a given neural drive, oesophageal pressure during apnoeic episodes may differ from that during airflow, since inspiratory airflow and increased lung volume both reduce pressure generation. It was, therefore, hypothesised that diaphragm electromyography (EMG) may provide additional data to oesophageal pressure when used for the assessment of neural drive in patients with obstructive sleep apnoea, whose breathing is associated with variable airflow and changes in lung volume.

Neural respiratory drive was assessed using diaphragm EMG recorded from multipair oesophageal electrodes in 12 patients with obstructive sleep apnoea. Oesophageal pressure was also recorded.

The mean±sdinspiratory oesophageal pressure swing was 11.0±3.7 cmH2O during wakefulness, 38.2±15.7 cmH2O at the end of the apnoea and reduced to 28.5±10.4 cmH2O at the beginning of arousal. The mean peak inspiratory diaphragm EMG signal was 21.8±6.5 μV during wakefulness, 38.6±14.0 μV at the end of the apnoea and further increased to 59.6±32.0 μV at the beginning of arousal.

It was concluded that the pattern of neural drive assessed by oesophageal pressure differs from that measured by diaphragm electromyography during apnoeic events and, therefore, that diaphragm electromyography may be a useful adjunct to measurement of oesophageal pressure for the assessment of neural drive in patients with obstructive sleep apnoea.
Effects of allergen on airway narrowing dynamics as assessed by lung-slice technique
Authors: Chew A. D. , Hirota J. A. , Ellis R. , Wattie J. , Inman M. D. , Janssen L. J.
Published: November 2007

Asthma is characterised by an excessive airway narrowing in response to a variety of stimuli, called airway hyperresponsiveness (AHR). Previous comparisons between mouse strains have shown that increased velocity of airway narrowing correlates with baseline airway responsiveness. These data prompted the investigation into models of induced AHR to see whether airway narrowing dynamics correlated within vivoresponsiveness.

In an attempt to reproduce some of the features of asthma, BALB/c mice were sensitised and subjected to either brief or chronic periods of allergen exposure. Brief exposure involved two challenges with intranasal chicken egg ovalbumin (OVAin). Chronic exposure involved six 2-day periods of OVAinchallenges, each separated by 12 days. Control mice received intranasal saline challenges. Outcomes included videomicrometry of lung slices (magnitude and velocity of airway narrowing),in vivorespiratory physiology measurements and histological staining with morphometric analysis.

Neither brief nor chronic allergen exposure resulted in greater airway narrowing and increased velocity compared with saline controls. Structural changes in the airway, such as goblet cell hyperplasia, subepithelial fibrosis and increased contractile tissue, were detected in mice chronically challenged with allergen.

In conclusion, increased responsiveness to methacholine following allergen challenge may not be due to an intrinsic change to the smooth muscleper se, but rather to other changes in the lung, which ultimately manifest as an increase in respiratory resistance.
Validity and reliability testing of two instruments to measure breast cancer patients' concerns and information needs relating to radiation therapy
Authors: Halkett Georgia KB , Kristjanson Linda J
Published: November 2007

Background

It is difficult to determine the most effective approach to patient education or tailor education interventions for patients in radiotherapy without tools that assess patients' specific radiation therapy information needs and concerns. Therefore, the aim of this study was to develop psychometrically sound tools to adequately determine the concerns and information needs of cancer patients during radiation therapy.

Patients and Methods

Two tools were developed to (1) determine patients concerns about radiation therapy (RT Concerns Scale) and (2) ascertain patient's information needs at different time point during their radiation therapy (RT Information Needs Scale). Tools were based on previous research by the authors, published literature on breast cancer and radiation therapy and information behaviour research. Thirty-one breast cancer patients completed the questionnaire on one occasion and thirty participants completed the questionnaire on a second occasion to facilitate test-retest reliability. One participant's responses were removed from the analysis. Results were analysed for content validity, internal consistency and stability over time.

Results

Both tools demonstrated high internal consistency and adequate stability over time. The nine items in the RT Concerns Scale were retained because they met all pre-set psychometric criteria. Two items were deleted from the RT Information Needs Scale because they did not meet content validity criteria and did not achieve pre-specified criteria for internal consistency. This tool now contains 22 items.

Conclusion

This paper provides preliminary data suggesting that the two tools presented are reliable and valid and would be suitable for use in trials or in the clinical setting.
International Web-based consultation on priorities for translational breast cancer research
Authors: Dowsett Mitch , Goldhirsch Aron , Hayes Daniel F , Senn Hans-Joerg , Wood William , Viale Giuseppe
Published: November 2007

Background

Large numbers of translational breast cancer research topics have been completed or are underway, but they differ widely in their immediate and/or future importance to clinical management. We therefore conducted an international Web-based consultation of breast cancer professionals to identify the topics most widely considered to be of highest priority.

Methods

Potential participants were contacted via two large e-mail databases and asked to register, at a Web site, the issues that they felt to be of highest priority. Four hundred nine questions were reduced by a steering committee to 70 unique issues, and registrants were asked to select the 6 questions they considered to be the most important.

Results

Votes were recorded from 420 voters (2,520 votes) from 48 countries, with 48% of voters coming from North America. Half of the voters identified themselves as clinicians, with the remainder being academics, research scientists, or pathologists. The highest priority was to identify molecular signatures to select patients who could be spared chemotherapy, which gained about 50% more votes than the second topic and was consistently voted top by voters in North America, Europe, and the rest of the world. Research scientists voted the determination of the role of stem cells in breast cancer development, progression, and treatment sensitivity as the most important issue, but this was considered the sixth priority for clinicians and fourth overall.

Conclusion

This exercise may bring a greater focus of research resources onto issues voted as top priorities.
CellFrame: A Data Structure for Abstraction of Cell Biology Experiments and Construction of Perturbation Networks
Authors: GONG YUNCHEN , ZHANG ZHAOLEI
Published: November 2007

Abstract:  Different cell types could respond to the same set of stimuli in very different ways, so it is important to collect and integrate these experimental data in a cell‐type specific manner in order to properly model these processes. In practice, however, cellular or biochemical models were usually constructed separately, with data from multiple cell sources, making it difficult to compare or combine these models. To circumvent this problem, we propose to conduct the model integration at the data level. To facilitate this purpose we have designed a data structure (CellFrame) to store cell‐specific data, such as cellular component measurement and stimulus‐response, and to infer cell perturbation network (a cellular network representing the stimulus–response relationships between the cellular and/or environmental components). The CellFrame database consists of two data types: data classes and supporting classes. Data classes constitute three modules: cell component measurement, qualitative cell perturbation, and quantitative cell perturbation. Supporting classes serve as adaptors, linking to external molecular or literature databases. We have implemented an initial version of CellFrame, which contains data collected from reported experiments on human brain astrocytoma and colorectal cancer cell lines (http://cellframe.bioknowledge.org). Perturbation networks are inferred following Boolean differential calculus. CellFrame will provide an opportunity to integrate cell biological data from a wide variety of experimental groups to help build cell models and design further experiments.
ENFIN—a Network to Enhance Integrative Systems Biology
Authors: KAHLEM PASCAL , BIRNEY EWAN
Published: November 2007

Abstract:  Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing both an adapted infrastructure to connect databases and platforms to enable the generation of new bioinformatics tools as well as the experimental validation of computational predictions. We will give an overview of the projects tackled within ENFIN and discuss the challenges associated with integration for systems biology.
Reconstructing Signal Transduction Pathways
Authors: LEVINE ARNOLD J. , HU WENWEI , FENG ZHAOHUI , GIL GERMAN
Published: November 2007

Abstract:  In this chapter, we will review how signal transduction pathways have been assembled in the past, bringing us to our present understanding of this area of research. The methods employed have relied heavily upon the genetics of yeast, worms, flies, mice, and humans. The use of second site suppressors and epistasis has permitted the detection of interacting elements and the sequence of genetic activities. Biochemistry has been employed to elucidate metabolic pathways, demonstrate protein complexes, and identify functions of gene products. The tools of molecular biology—knocking concentration of protein products down or up—have been helpful to trace the function of pathways in vivo. The study of disease states has led to the identification of a set of altered genes and helped define a network that is altered and gives rise to the disease. We will also discuss some serious limitations in these approaches. After reviewing how signal transduction pathways are constructed and investigated, we will turn our attention to an example that demonstrates the inter‐relationships between pathways and the regulation of a specific set of pathways. We will examine how the p53 pathway in responding to stress shuts down the AKT‐1 and mTOR pathways so as to limit the error frequency of cell growth and division during a stressful time where homeostatic mechanisms are required to respond and increase the fidelity of these processes.
Patients' concerns about and problems experienced with discontinuation of antidepressants
Authors: Van Geffen E C G , Brugman M , Van Hulten R , Bouvy M L , Egberts A C G , Heerdink E R
Published: November 2007

Objective

Clinical trials and epidemiological studies have shown that premature discontinuation is a major problem during antidepressant therapy. Unfortunately, there is little information on how patients perceive treatment with antidepressants in clinical practice, and it is unclear whether patients perceive discontinuation as a problem. The objective of this study is to assess whether concerns and problems experienced with drug discontinuation occur more frequently in patients using antidepressants than in patients using benzodiazepines, antipsychotics or non-psychiatric medication.

Method

All calls to a national telephone medicines information service received between 1990 and 2004 were examined using retrospective examination. Calls about discontinuation were identified and classified either as a general question about discontinuation, or as a problem experienced with discontinuation. These calls were grouped into the following main classes: antidepressants, antipsychotics, benzodiazepines or non-psychiatric medicines.

Key findings

Of all 39 786 registered phone calls, 6159 (15,5%) related to antidepressants, 1658 (4.2%) to antipsychotics and 3916 (9.8%) to benzodiazepines. Patients calling about antidepressants called about discontinuation three times as often (odds ratio (OR) 2.8; 95% confidence interval (CI) 2.6–3.0), and reported a problem with discontinuation five times more often (OR 5.4; 95% CI 4.6–6.3), compared to patients who called about non-psychiatric medicines. The proportion of questions about discontinuation and problems experienced with discontinuation was also higher in patients calling about benzodiazepines and antipsychotics compared to patients calling about non-psychiatric medication.

Conclusion

Patients perceive discontinuation of antidepressants, as well as discontinuation of antipsychotics and benzodiazepines, as a problem. Discontinuation seems a general problem for all psychiatric medicines, and needs more attention in the communication between patients and healthcare providers.
Potentiating effect of β-caryophyllene on anticancer activity of α-humulene, isocaryophyllene and paclitaxel
Authors: Legault Jean , Pichette André
Published: November 2007

β-caryophyllene is a sesquiterpene widely distributed in essential oils of various plants. Several biological activities are attributed to β-caryophyllene, such as anti-inflammatory, antibiotic, antioxidant, anticarcinogenic and local anaesthetic activities. In this work, the potentiating effect of β-caryophyllene on the anticancer activity of α-humulene, isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell lines was evaluated. A non-cytotoxic concentration of β-caryophyllene significantly increased the anticancer activity of α-humulene and isocaryophyllene on MCF-7 cells: α-humulene or isocaryophyllene alone (32 μg mL−1) inhibited cell growth by about 50% and 69%, respectively, compared with 75% and 90% when combined with 10 μg mL−1 β-caryophyllene. Moreover, β-caryophyllene potentiated the anticancer activity of paclitaxel on MCF-7, DLD-1 and L-929 cell lines. The highest potentiating effect was obtained in DLD-1 cells treated with paclitaxel combined with 10 μg mL−1 β-caryophyllene, which increased the paclitaxel activity about 10-fold. The intracellular accumulation of paclitaxel-oregon green was evaluated in combination with concentrations of β-caryophyllene ranging from 2.5 to 40 μg mL−1. β-Caryophyllene (10 μg mL−1) significantly increased the intracellular accumulation of paclitaxel-oregon green (about 64% over controls). Moreover, β-caryophyllene induced intracellular accumulation of calcein but not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related protein transporters, suggesting that β-caryophyllene promotes drug accumulation by a different mechanism of action. These results suggest that β-caryophyllene facilitates the passage of paclitaxel through the membrane and thus potentiates its anticancer activity.
Substituted tetrahydroisoquinoline compound B3 inhibited P-glycoprotein-mediated multidrug resistance in-vitro and in-vivo
Authors: Fang Weirong , Li Yunman , Cai Ying , Kang Kai , Yan Fang , Liu Guoqing , Huang Wenlong
Published: November 2007

P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is one of the main obstacles in tumour chemotherapy. A promising approach to reverse MDR is the combined use of nontoxic and potent P-gp inhibitor with conventional anticancer drugs. We have examined the potential of a newly synthesized tetrahydroisoquinoline derivative B3 as a MDR-reversing agent. The MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to examine the effect of B3 on the cytotoxicity in K562/A02 and MCF-7/ADM cells caused by doxorubicin (adriamycin). Accumulation and efflux of P-gp substrate rhodamine123 in K562/A02 and primary cultured rat brain microvessel endothelial cells (RBMECs) were measured to evaluate the inhibitory effect of B3 on P-gp. The K562/A02 xenograft model in nude mice was established to examine MDR-reversing efficacy of B3 in-vivo. The results indicated that co-administration of B3 resulted in an increase on chemosensitivity of K562/A02 and MCF-7/ADM cells to doxorubicin in a dose-dependent manner. Rhodamine123 accumulation in K562/A02 cells and RBMECs were significantly enhanced after the incubation with various concentrations of B3. Furthermore, B3 inhibited the efflux of rhodamine123 from RBMECs. Co-administration of B3 with doxorubicin significantly decreased weight and volume of tumour in nude mice. In conclusion, B3 is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumour chemotherapy.
Bicyclol, a synthetic dibenzocyclooctadiene derivative, decreases hepatic lipids but increases serum triglyceride level in normal and hypercholesterolaemic mice
Authors: Pan Si-Yuan , Dong Hang , Yu Zhi-Ling , Zhao Xin-Ye , Xiang Chun-Jing , Wang Hui , Fong Wang-Fun , Ko Kam-Ming
Published: November 2007

Bicyclol is used for the treatment of chronic hepatitis B in China. In this study, the effects of bicyclol (100 or 300 mg kg−1, p.o.) on serum and liver lipid contents were investigated in both normal and experimentally induced hypercholesterolaemic mice. Hypercholesterolaemia was induced by either oral administration of cholesterol/bile salt or feeding a diet containing lard/cholesterol. Daily administration of bicyclol for 7 days dose-dependently increased the serum triglyceride level (29–80%) but slightly decreased the hepatic total cholesterol level (12–17%) in normal mice. Co-administration of bicyclol with cholesterol/bile salt decreased the hepatic triglyceride and total cholesterol levels (7–15% and 25–31%, respectively), when compared with the drug-untreated and cholesterol/bile salt-treated group. Bicyclol treatment for 7 days decreased hepatic triglyceride (5–76%) and total cholesterol (5–48%) levels in mice fed with high-fat/cholesterol diet. In contrast, bicyclol treatment increased the serum triglyceride level (18–77%) in mice treated with cholesterol/bile salt or fed with high-fat/cholesterol diet. Bicyclol treatment also caused an increase in hepatic index of normal and hypercholesterolaemic mice (3–32%). The results indicate that bicyclol treatment can invariably decrease hepatic lipid levels and increase serum triglyceride levels in normal and hypercholesterolaemic mice.
In-vivo and in-vitro studies on the effect of Huang-Lian-Jie-Du-Tang on nimodipine transport across rat blood-brain barrier
Authors: Zhang Dong Mei , He Zhen Wei , Liu Xiao Dong , Li Yang , Xie Lin , Wang Guang Ji , Liu Li
Published: November 2007

Huang-Lian-Jie-Du-Tang (HLJDT), an aqueous extract of Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae (3:2:2:3) is an important multi-herb remedy in traditional Chinese medicine (TCM). The aim of this study was to evaluate the effect of HLJDT on nimodipine transport across rat blood-brain barrier (BBB). It was found that in-vivo the brain concentrations of nimodipine significantly increased when rats were pretreated with HLJDT. In-vitro, the serum of HLJDT-treated rats increased the accumulation of nimodipine in primary cultured rat brain micro-vessel endothelial cells (rBMECs) and decreased the expression of P-glycoprotein (P-gp) on rBMECs. Our previous study showed that the peak concentration of baicalin and berberine in rats after administration of HLJDT was 5 μg mL−1 and 10 ng mL−1, respectively. This study showed that 5 μg mL−1 baicalin significantly increased the accumulation of nimodipine in rBMECs, while 10 ng mL−1 berberine had no effect on the accumulation of nimodipine in rBMECs. Both the in-vivo and in-vitro experimental findings indicated that HLJDT pretreatment may alter the transport of nimodipine across rat BBB.
Modulatory effect of seabuckthorn leaf extract on oxidative stress parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery
Authors: Saggu Shalini , Kumar Ratan
Published: November 2007

This study was carried out to examine the antioxidative potential, if any, of seabuckthorn leaf aqueous extract, administered orally in rats at a dose of 100 mg kg−1 both in single and five doses, 30 min before cold (5°C)–hypoxia (428 mm Hg)–restraint (C-H-R) exposure. The effect of the extract was studied on lipid peroxidation and antioxidant parameters in liver and gastrocnemius muscle of rats on attaining the rectal temperature (Trec) of 23°C during C-H-R exposure and after recovery (Trec37°C) from C-H-R-induced hypothermia. In untreated rats exposed to C-H-R, there was a significant increase in malondialdehyde (MDA) levels in liver and muscle along with decreased activity of catalase (CAT) and glutathione-S-transferase (GST) in liver and muscle. Single- and five-dose extract treatment restricted the increase in liver and muscle MDA levels and five doses of extract treatment further improved the levels of liver antioxidants, viz. reduced glutathione (GSH), on recovery of Trec37°C, increased superoxide dismutase (SOD) during exposure and recovery, normalized CAT activity in liver during C-H-R exposure and an increase on recovery of Trec37°C. The decreasing pattern of liver and muscle GST levels both in single-dose and five-dose extract treated rats was similar to that in untreated rats. Results suggested that supplementation with seabuckthorn extract helps to reduce oxidative stress in liver and muscle of rats during C-H-R exposure and post-stress recovery.
Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2
Authors: Takatori Atsushi , Geh Esmond , Chen Liang , Zhang Lin , Meller Jarek , Xia Ying
Published: November 2007

JNK1 and JNK2 are two ubiquitously expressed isoforms that exert redundant roles in many physiological processes, but the extent of their relative contributions to these processes has not been well characterized. We show that both JNK isoforms transmit MEK kinase 1 (MEKK1)-mediated morphogenetic signals during mouse embryonic eyelid closure. However, JNK1 and JNK2 are not synonymous, because MEKK1 is haploinsufficient for normal eyelid closure in Jnk1-null mice, but is haplosufficient in Jnk2-null mice. In the Mekk1 heterozygous background, a more efficient phosphorylation of JNK1 than JNK2 leads to differential downstream reactions, such as c-Jun phosphorylation and PAI1 expression in the developing eyelid epithelium. Differences in efficiency of phosphorylation are attributed to JNK1 Gly177 and Ser179 - residues that are absent in JNK2 - which promote a less ordered structural conformation. This leads to more favorable JNK phosphorylation by activin B morphogenetic signals mediated by the MEKK1-MKK4 pathway. Interestingly, Mekk1-Jnk1-Jnk2 triple hemizygotes display a partial eye-open phenotype at birth, suggesting that all three genes dose-dependently contribute to morphogenetic eyelid closure. We propose that a MEKK1-JNK1/2 axis governs the JNK activation levels to control downstream transcriptional events and eyelid morphogenesis and that reduction of upstream MEKK1 signals uncovers analogous but differential roles of JNK1 and JNK2 in a biological process.