bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Infant Feeding Activity and Nutrition Trial (INFANT) an early intervention to prevent childhood obesity: Cluster-randomised controlled trial
Authors: Campbell Karen , Hesketh Kylie , Crawford David , Salmon Jo , Ball Kylie , McCallum Zoë 
Published: April 2008

AbstractBackgroundMultiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour) from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT) aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant's first 18 months of life, will use existing social networks (first-time parent's groups) and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy.Methods/DesignThis cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents' group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group.DiscussionThe early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups promotes healthy eating, physical activity and reduced sedentary behaviours. If proven to be effective, INFANT may protect children from the development of obesity and its associated social and economic costs.Trial registrationCurrent Controlled Trials ISRCTN81847050
Verifiability of diagnostic categories and work ability in the context of disability pension award: A survey on "gatekeeping" among general practitioners in Norway
Authors: Overland Rein , Overland Simon , Johansen Kristian Nyborg , Mykletun Arnstein 
Published: April 2008

Abstract

Background
Disability benefits exist to redeem social and financial consequences of reduced work ability from medical conditions. Physicians are responsible for identifying the medical grounds for benefit claims. The aim of this study was to explore physicians' views on verifiability of medical conditions and related work ability in this context.

Methods
Information on verifiability of diagnostic categories and work ability was obtained from a survey among a representative sample of general practitioners (GPs) in Norway (n = 500, 25.2% response rate). Verifiability was defined as to what extent the assessment is based on objective criteria versus on information from the patient. We enquired about the diagnostic categories used in official statistics on main disability benefit causes in Norway and elsewhere.

Results
On a scale from 0 (low verifiability) to 5 (high verifiability), the mean level of verifiability across all diagnostic categories was 3.7 (SD = 0.42). Degree of verifiability varied much between diagnostic categories, and was low in e.g. unspecified rheumatism/myalgia and dorsopathies, and high in neoplasms and congenital malformations, deformation and chromosomal abnormalities. Verifiability of work ability was reported to be more problematic than that of diagnostic categories. The diagnostic categories rated as the least verifiable, are also the most common in disability pension awards.

Conclusion
Verifiability of both diagnostic categories and work ability in disability assessments are reported to be moderate by GPs. We suggest that the low verifiability of diagnostic categories and related work ability assessments in the majority of disability pension awards is important in explaining why GPs find the gatekeeping-function problematic.
Use of a commercial enzyme immunoassay to monitor dengue virus replication in cultured cells
Authors: Ludert Juan E , Mosso Clemente , Ceballos-Olvera Ivonne , del Angel Rosa M 
Published: April 2008

AbstractCurrent methods for dengue virus quantitation are either time consuming, technically demanding or costly. As an alternative, the commercial enzyme immunoassay Platelia™ Dengue NS1 AG (Bio-Rad Laboratories) was used to monitor semiquantitatively dengue virus replication in cultured cells. The presence of NS1 protein was evaluated in supernatants from Vero and C6/36 HT cells infected with dengue virus. The amount of NS1 detected in the supernatants of infected cells was proportional to the initial MOI used and to the time of post infection harvest. This immunoassay was also able to detect the presence of NS1 in the supernatants of infected human macrophages. Inhibition of dengue virus replication in C6/36 HT cells treated with lysosomotropic drugs was readily monitored with the use of this assay. These results suggest that the Platelia™ Dengue NS1 AG kit can be used as a fast and reliable surrogate method for the relative quantitation of dengue virus replication in cultured cells.
Phenotype prediction in regulated metabolic networks
Authors: Kaleta Christoph , Centler Florian , di Fenizio Pietro Speroni , Dittrich Peter 
Published: April 2008

AbstractBackgroundDue to the growing amount of biological knowledge that is incorporated into metabolic network models, their analysis has become more and more challenging. Here, we examine the capabilities of the recently introduced chemical organization theory (OT) to ease this task. Considering only network stoichiometry, the theory allows the prediction of all potentially persistent species sets and therewith rigorously relates the structure of a network to its potential dynamics. By this, the phenotypes implied by a metabolic network can be predicted without the need for explicit knowledge of the detailed reaction kinetics.ResultsWe propose an approach to deal with regulation – and especially inhibitory interactions – in chemical organization theory. One advantage of this approach is that the metabolic network and its regulation are represented in an integrated way as one reaction network. To demonstrate the feasibility of this approach we examine a model by Covert and Palsson (J Biol Chem, 277(31), 2002) of the central metabolism ofE. colithat incorporates the regulation of all involved genes. Our method correctly predicts the known growth phenotypes on 16 different substrates. Without specific assumptions, organization theory correctly predicts the lethality of knockout experiments in 101 out of 116 cases. Taking into account the same model specific assumptions as in the regulatory flux balance analysis (rFBA) by Covert and Palsson, the same performance is achieved (106 correctly predicted cases). Two model specific assumptions had to be considered: first, we have to assume that secreted molecules do not influence the regulatory system, and second, that metabolites with increasing concentrations indicate a lethal state.ConclusionThe introduced approach to model a metabolic network and its regulation in an integrated way as one reaction network makes organization analysis a universal technique to study the potential behavior of biological network models. Applying multiple methods like OT and rFBA is shown to be valuable to uncover critical assumptions and helps to improve model coherence.
A systems biology approach to analyse amplification in the JAK2-STAT5 signalling pathway
Authors: Vera Julio , Bachmann Julie , Pfeifer Andrea C , Becker Verena , Hormiga Jose A , Darias Nestor V Torres , Timmer Jens , Klingmüller Ursula , Wolkenhauer Olaf 
Published: April 2008

Abstract

Background
The amplification of signals, defined as an increase in the intensity of a signal through networks of intracellular reactions, is considered one of the essential properties in many cell signalling pathways. Despite of the apparent importance of signal amplification, there have been few attempts to formalise this concept.

Results
In this work we investigate the amplification and responsiveness of the JAK2-STAT5 pathway using a kinetic model. The recruitment of EpoR to the plasma membrane, activation by Epo, and deactivation of the EpoR/JAK2 complex are considered as well as the activation and nucleocytoplasmic shuttling of STAT5. Using qualitative biological knowledge, we first establish the structure of a general power-law model. We then generate a family of models from which we select suitable candidates. The parameter values of the model are estimated from experimental quantitative time-course data. The final model, whether it is conventional model with fixed predefined integer kinetic orders or a model with variable non-integer kinetic orders, is selected on the basis of a good agreement between simulations and the experimental data. The model is used to analyse the responsiveness and amplification properties of the pathway with sustained, transient, and oscillatory stimulation.

Conclusion
The selected kinetic model predicts that the system acts as an amplifier with maximum amplification and sensitivity for input signals whose intensity match physiological values for Epo concentration and with duration in the range of one to 100 minutes. The response of the system reaches saturation for more intense and longer stimulation with Epo. We hypothesise that these properties of the system directly relate to the saturation of Epo receptor activation, its low recruitment to the plasma membrane and intense deactivation as predicted by the model.
Evolutionary potentials: structure specific knowledge-based potentials exploiting the evolutionary record of sequence homologs
Authors: Panjkovich Alejandro , Melo Francisco , Marti-Renom Marc A 
Published: April 2008

AbstractWe introduce a new type of knowledge-based potentials for protein structure prediction, called 'evolutionary potentials', which are derived using a single experimental protein structure and all three-dimensional models of its homologous sequences. The new potentials have been benchmarked against other knowledge-based potentials, resulting in a significant increase in accuracy for model assessment. In contrast to standard knowledge-based potentials, we propose that evolutionary potentials capture key determinants of thermodynamic stability and specific sequence constraints required for fast folding.
The acute phase protein haptoglobin regulates host immunity
Authors: Huntoon Kristin M , Wang Yanping , Eppolito Cheryl A , Barbour Karen W , Berger Franklin G , Shrikant Protul A , Baumann Heinz 
Published: April 2008

AbstractThe contribution of acute phase plasma proteins to host immune responses remains poorly characterized. To better understand the role of the acute phase reactant and major hemoglobin-binding protein haptoglobin (Hp) on the function of immune cells, we generated Hp-deficient C57BL/6J mice. These mice exhibit stunted development of lymphoid organs associated with lower counts of mature T and B cells in the blood and secondary lymphoid compartments. Moreover, these mice show markedly reduced adaptive immune responses as represented by reduced accumulation of IgG antibody after immunization with adjuvant and nominal antigen, abrogation of Th1-dominated delayed-type hypersensitivity reaction, loss of mitogenic responses mounted by T cells, and reduced T cell responses conveyed by APCs. Collectively, these defects are in agreement with the observations that Hp-deficient mice are not capable of generating a recall response or deterring a Salmonella infection as well as failing to generate tumor antigen-specific responses. The administration of Hp to lymphocytes in tissue culture partially ameliorates these functional defects, lending further support to our contention that the acute phase response protein Hp has the ability to regulate immune cell responses and host immunity. The phenotype of Hp-deficient mice suggests a major regulatory activity for Hp in supporting proliferation and functional differentiation of B and T cells as part of homeostasis and in response to antigen stimulation.
Murine gammaherpesvirus-induced fibrosis is associated with the development of alternatively activated macrophages
Authors: Gangadharan Babunilayam , Hoeve Marieke A , Allen Judith E , Ebrahimi Bahram , Rhind Susan M , Dutia Bernadette M , Nash Anthony A 
Published: April 2008

AbstractMurine gammaherpesvirus 68 (MHV-68) is a natural pathogen of rodents closely related to the human γherpesviruses Kaposi’s sarcoma-associated herpesvirus and EBV. Following intranasal infection, the virus replicates in the lung epithelium prior to establishing latent infection in lymphoid tissue. Infection of mice deficient in IFN-γR signaling (IFN-γR−/−) results in a multiple organ fibrosis, in which the spleen is severely affected. We show here that by Day 12 postinfection, prior to development of fibrosis in the spleens of IFN-γR−/− mice, different subsets of splenic macrophages (Mϕs) are morphologically activated and enter latently infected germinal centers (GCs). Mϕs coexpressing arginase I (ARG1), a marker of alternative activation of Mϕs, and murine Mϕ markers F4/80, ER-TR9, and MOMA-1 are found in GCs of IFN-γR−/− mice but not of wild-type mice. Quantitative RT-PCR of spleen RNA confirms induction of ARG1 and in addition, shows up-regulation of found in inflammatory zone 1/resistin-like molecule-α, tissue inhibitor of metalloproteinase-1, matrix metalloproteinase-12, fibronectin, and factor XIIIA in IFN-γR−/− mice. In contrast, inducible NO synthase, associated with classical Mϕ activation, is up-regulated following infection of wild-type mice but not IFN-γR−/− mice. Concomitant with the aaMϕs, transcription of the Th2 cytokines IL-13, IL-21, and IL-5 is up-regulated. Thus, in the absence of IFN-γR signaling, MHV-68 initiates a Th2 immune response, leading to alternative activation of macrophages and induction of fibrosis. This system provides an important model for studying the pathogenesis of fibrosis initiated by a latent herpesvirus infection.
Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration
Authors: Popovic Milan , Laumonnier Yves , Burysek Ladislav , Syrovets Tatiana , Simmet Thomas 
Published: April 2008

AbstractCX3CL1 (fractalkine, neurotactin) is the sole CX3C chemokine. It induces monocyte locomotion in its cleaved form, but in its membrane-anchored form, it also acts as an adhesion molecule. The expression of CX3CL1 is up-regulated in endothelial cells by proinflammatory cytokines such as IL-1 or TNF-α. Here, we studied the effect of the serine protease thrombin on endothelial CX3CL1 induction and its putative relevance for monocyte function. In HUVEC, thrombin triggered a time- and concentration-dependent expression of CX3CL1 at the mRNA and the protein level as shown by RT-PCR, Western immunoblotting, and flow cytometric analysis. Thrombin induced CX3CL1 by activating protease-activated receptor 1 (PAR1) as demonstrated by the use of PAR1-activating peptide and the PAR1-specific antagonist SCH 79797. The thrombin-induced CX3CL1 expression was NF-κB-dependent, as shown by EMSA, ELISA, and by inhibition of the NF-κB signaling pathway by the IκB kinase inhibitor acety-11-keto-β-boswellic acid or by transient overexpression of a transdominant-negative form of IκBα. Upon cocultivation of human monocytes with HUVEC, the thrombin-dependent induction of membrane-anchored CX3CL1 in HUVEC triggered monocyte adhesion and an enhanced release of the MCP-1/CCL2 by monocytes and potentiated the monocyte transendothelial migration. Accordingly, the recombinant extracellular domain of CX3CL1 induced CCL2 release by monocytes. Thus, the thrombin-induced monocyte/endothelial cell cross-talk mediated by increased CX3CL1 expression potentiates the CCL2 chemokine generation that might contribute to the recruitment of monocytes into inflamed areas.
Enhanced susceptibility to Con A-induced liver injury in mice transgenic for the intracellular isoform of human TNF receptor type 2
Authors: Bäumel Monika , Lechner Anja , Hehlgans Thomas , Männel Daniela N 
Published: April 2008

AbstractTNF is a pleiotropic cytokine involved in a variety of inflammatory processes and immune responses. TNF effects are mediated via two distinct membrane receptors: TNFR1 and TNFR2. Investigations concerning regulation and function of TNFR2 revealed a novel TNFR2 isoform in human and mouse cells, termed icp75TNFR, with mainly intracellular localization. As human icp75TNFR is capable of functional interaction with mouse TNF, mouse lines transgenic for the human icp75TNFR were generated and characterized. Transgenic expression was identified in several organs, and soluble human (sh)TNFR2 was detected in serum. shTNFR2 released from transfected cells or peritoneal macrophages of transgenic mice protected from TNF-induced cytotoxicity. Although in vivo, no change in inflammatory reactions was observed in models of septic peritonitis, of colitis, or after stimulation with bacterial LPS, liver injury was strongly enhanced in transgenic mice after Con A challenge. Thus, the functional properties of human icp75TNFR seem to be similar to that of TNFR2, resulting in exacerbation of inflammatory tissue damage, thus revealing the functional importance of TNFR2 in pathophysiological processes.
Transcriptional profiling of human skin-resident Langerhans cells and CD1a+ dermal dendritic cells: differential activation states suggest distinct functions
Authors: Santegoets Saskia J A M , Gibbs Susan , Kroeze Kim , van de Ven Rieneke , Scheper Rik J , Borrebaeck Carl A , de Gruijl Tanja D , Lindstedt Malin 
Published: April 2008

AbstractIn human skin, two main populations of dendritic cells (DC) can be discriminated: dermal DC (DDC) and epidermal Langerhans cells (LC). Although extensively studied, most of the knowledge about DDC and LC phenotype and function is obtained from studying DDC and LC cultured in vitro or DDC and LC migrated from skin explants. These studies have left the exact relationship between steady-state human LC and DDC unclear: in particular, whether CD1a+ DDC represent migrated LC or whether they constitute a separate subset. To gain further insight in the kinship between skin-resident CD1a+ DDC and LC, we analyzed CD1a+ DDC and LC, isolated from steady-state skin samples, by high-density microarray analysis. Results show that the CD1a+ DDC specifically express markers associated with DDC phenotype, such as the macrophage mannose receptor, DC-specific ICAM-grabbing nonintegrin, the scavenger receptor CD36, coagulation factor XIIIa, and chemokine receptor CCR5, whereas LC specifically express Langerin, membrane ATPase (CD39), and CCR6, all hallmarks of the LC lineage. In addition, under steady-state conditions, both DC subsets display a strikingly different activation status, indicative of distinct functional properties. CD1a+ DDC exhibit a more activated, proinflammatory, migratory, and T cell-stimulatory profile, as compared with LC, whereas LC mainly express molecules involved in cell adhesion and DC retention in the epidermis. In conclusion, transcriptional profiling is consistent with the notion that CD1a+ DDC and LC represent two distinct DC subsets but also that under steady-state conditions, CD1a+ DDC and epidermal LC represent opposites of the DC activation spectrum.
Illness and treatment cognitions and health related quality of life in end stage renal disease
Authors: Griva Konstadina , Jayasena Dakshina , Davenport Andrew , Harrison Michael , Newman Stanton P. 
Published: April 2008

Objectives. Patients' beliefs regarding illness and treatment are important to understand responses to chronic disease. The present study aimed (i) to assess the illness representations and treatment disruption beliefs of patients with end stage renal disease (ESRD), (ii) to determine whether beliefs about illness and treatment differ between different renal replacement therapies, and (iii) to examine whether these beliefs are associated with health related quality of life (HQoL).Method. A cross‐sectional sample of 262 ESRD patients, 145 dialysis and 117 kidney transplant recipients completed the illness perceptions questionnaire, the illness effects questionnaire, the treatment effects questionnaire and the short form 36 health survey. Measures of ESRD severity/co‐morbidity and biochemistry were also collected.Results. HQoL levels were higher in transplant patients. Dialysis patients reported more symptoms associated with ESRD (p<.001), stronger chronic timeline beliefs (p<.001), lower control beliefs (p<.05), and more illness and treatment disruptiveness (ps<.01). Illness and treatment disruptiveness, consequences and identity were inversely associated with HQoL whereas control was positively associated with HQoL. Multiple regressions indicated that treatment and illness disruptiveness, identity and consequences beliefs accounted for 22.9–67.6% of the variance HQoL although specific multivariate correlates differed across physical and emotional HQoL and between dialysis and transplantation.Conclusions. The beliefs that patients hold about their illness and treatment appear to be related to the type renal replacement therapy being undertaken. These cognitions have associations with HQoL in dialysis and transplantation that are independent of those of socio‐demographic and clinical factors.
Cognitive and social processes predicting partner psychological adaptation to early stage breast cancer
Authors: Manne Sharon , Ostroff Jamie , Fox Kevin , Grana Generosa , Winkel Gary 
Published: April 2008

Introduction. The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners' psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined.Materials and methods. Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner's diagnosis (N=253), 9 (N=167), and 18 months (N=149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning making, and general and cancer‐specific distress at all time points.Results. Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer‐specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer‐specific distress were found.Conclusions. Results indicate several cognitive–social processes directly predict partner distress. However, moderator effect models in which the effects of partners' processing depends upon whether these efforts result in changes in perceptions of the cancer experience may add to the understanding of partners' adaptation to cancer.