bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of inhaled and oral corticosteroids on serum inflammatory biomarkers in COPD: an exploratory study
Authors: Man S.F. Paul , Xuekui Zhang  , Vessey Rupert , Walker Terry , Lee Kwan , Park Dan , Sin Don D. 
Published: May 2009

Background: Several studies suggest that inhaled and oral corticosteroids repress systemic inflammation in chronic obstructive pulmonary disease (COPD). However, the cytokines that may respond to these medications are unclear. Method: We used data from 41 patients with a history of stable moderate COPD (average age 64 years) who were randomised to inhaled fluticasone (500 μg twice daily from a Diskus inhaler), oral prednisone (30 mg daily) or placebo for 2 weeks. Using a multiplexed array system, different serum cytokines that have been implicated in COPD pathogenesis were measured. Results: We found that compared with placebo, inhaled fluticasone significantly reduced levels of soluble tumour necrosis factor receptor-2 (sTNF-R2) by 24% (95% CI, 7—38%; p = 0.01), monocyte chemoattractant protein-1 by 20% (95% CI, 5—32%; p = 0.01), interferon gamma inducible CXCL10 (IP-10) by 43% (95% CI, 3—66%; p = 0.04), and soluble L-selectin levels by 15% (95% CI, 1—28%; p = 0.04). Compared with placebo, oral prednisone reduced levels of sTNF-R2 by 26% (95% CI, 15—36%; p < 0.001), L-selectin by 22% (95% CI, 8—34%; p = 0.004), intercellular adhesion molecule-1 by 31% (95% CI, 9—48%; p = 0.01), pulmonary and activation-regulated chemokine (PARC) by 18% (95% CI, 2—32%; p = 0.03) and IP-10 by 40% (95% CI, 0—64%; p = 0.05). sTNF-R2, L-selectin and IP-10 were significantly reduced by both oral and inhaled corticosteroids. The other cytokines were not significantly repressed by either oral or inhaled corticosteroids. Conclusions: In summary, inhaled and oral corticosteroids significantly repressed a selected number of systemic cytokines in patients with stable, moderate COPD; most of the steroid-responsive cytokines appear to be chemoattractants.
The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis
Authors: Kingston Dior , Schmid Michael A. , Onai Nobuyuki , Obata-Onai Aya , Baumjohann Dirk , Manz Markus G. 
Published: May 2009

AbstractDendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are not defined. Here, we show that, although Gm-csfr and Flt3 are both expressed in DC progenitors, Gm-csfr is expressed predominantly in monocytes, classical DCs (cDCs), and skin DCs, whereas Flt3 is expressed in both cDCs and plasmacytoid DCs (pDCs). In accordance with the respective cytokine receptor expression, DC progenitor and pDC numbers are primarily affected by Flt3-ligand deficiency, whereas both splenic and lymph node cDCs and dermal DCs are reduced in the absence of either GM-CSF or Flt3-ligand. Combined lack of GM-CSF and Flt3-ligand in newly generated double-deficient mice leads to further significant reductions of DC progenitors and dermal DCs. In line with the decrease of respective DC subsets, T-cell and antigen-specific IgG responses decline progressively, from wild-type to GM-CSF– to Flt3-ligand– to double-deficient mice, upon subcutaneous antigen delivery. These data thus show the concerted action of GM-CSF and Flt3-ligand on DC homeostasis in vivo.
Orymold: ontology based gene expression data integration and analysis tool applied to rice
Authors: Mercadé Jaume , Espinosa Antonio , Adsuara José-Enrique , Adrados Rosa , Segura Jordi , Maes Tamara 
Published: May 2009

Abstract

Background
Integration and exploration of data obtained from genome wide monitoring technologies has become a major challenge for many bioinformaticists and biologists due to its heterogeneity and high dimensionality. A widely accepted approach to solve these issues has been the creation and use of controlled vocabularies (ontologies). Ontologies allow for the formalization of domain knowledge, which in turn enables generalization in the creation of querying interfaces as well as in the integration of heterogeneous data, providing both human and machine readable interfaces.

Results
We designed and implemented a software tool that allows investigators to create their own semantic model of an organism and to use it to dynamically integrate expression data obtained from DNA microarrays and other probe based technologies. The software provides tools to use the semantic model to postulate and validate of hypotheses on the spatial and temporal expression and function of genes. In order to illustrate the software's use and features, we used it to build a semantic model of rice (Oryza sativa) and integrated experimental data into it.

Conclusion
In this paper we describe the development and features of a flexible software application for dynamic gene expression data annotation, integration, and exploration called Orymold. Orymold is freely available for non-commercial users from http://www.oryzon.com/media/orymold.html
T cells cooperate with palmitic acid in induction of beta cell apoptosis
Authors: Cvjetićanin Tamara , Stojanović Ivana , Timotijević Gordana , Stošić-Grujičić Stanislava , Miljković Djordje 
Published: May 2009

Abstract

Background
Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction.

Results
Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3+ cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1β, interleukin-2, interleukin-6, interleukin-17, interferon-γ and tumor necrosis factor-α.

Conclusion
These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.
Polymorphism in COX-2 modifies the inverse association between Helicobacter pyloriseropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study
Authors: Hu Huang-Ming , Kuo Chao-Hung , Lee Chien-Hung , Wu I-Chen , Lee Ka-Wo , Lee Jang-Ming , Goan Yih-Gang , Chou Shah-Hwa , Kao Ein-Long , Wu Ming-Tsang , Wu Deng-Chyang 
Published: May 2009

Abstract

Background
Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC.

Methods
One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression.

Results
In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008)

Conclusion

H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus.
The Locomotor Capabilities Index; validity and reliability of the Swedish version in adults with lower limb amputation
Authors: Larsson Brita , Johannesson Anton , Andersson Ingemar H , Atroshi Isam 
Published: May 2009

AbstractBackgroundThe Locomotor Capabilities Index (LCI) is a validated measure of lower-limb amputees' ability to perform activities with prosthesis. We have developed the LCI Swedish version and evaluated its validity and reliability.MethodsCross-cultural adaptation to Swedish included forward/backward translations and field testing. The Swedish LCI was then administered to 144 amputees (55 women), mean age 74 (40–93) years, attending post-rehabilitation prosthetic training. Construct validity was assessed by examining the relationship between the LCI and Timed "Up-and-Go" (TUG) test and between the LCI and EQ-5D health utility index in 2 subgroups of 40 and 20 amputees, respectively. Discriminative validity was assessed by comparing scores in different age groups and in unilateral and bilateral amputees. Test-retest reliability (1–2 weeks) was evaluated in 20 amputees (14 unilateral).ResultsThe Swedish LCI showed good construct convergent validity, with high correlation with the TUG (r = -0.75) and the EQ-5D (r = 0.84), and discriminative validity, with significantly worse mean scores for older than younger and for bilateral than unilateral amputees (p < 0.01), and high internal consistency (Cronbach alpha 0.95). In test-retest reliability the intraclass correlation coefficient was 0.91 (95% CI 0.79–0.96) but for the unilateral amputees was 0.83 (95% CI 0.56–0.94). Ceiling effect occurred in 23%.ConclusionThe Swedish version of the LCI demonstrated good validity and internal consistency in adult amputees. Test-retest reliability in a small subsample appears to be acceptable. The high ceiling effect of the LCI may imply that it would be most useful in assessing amputees with low to moderate functional abilities.
Semaphorin 5B mediates synapse elimination in hippocampal neurons
Authors: O'Connor Timothy P , Cockburn Katie , Wang Wenyan , Tapia Lucia , Currie Erin , Bamji Shernaz X 
Published: May 2009

Abstract
Background
Semaphorins are known to play an important role in axon guidance and growth by triggering dynamic rearrangements of the actin cytoskeleton in the neuronal growth cone. Intriguingly, some of these guidance molecules are persistently expressed after axonal pathfinding and target recognition are completed. Although their function at these later stages is poorly understood, recent findings suggest a role for these proteins in regulating synaptic connections.

Results
Here we demonstrate that semaphorin 5B (Sema5B) regulates the elimination of synaptic connections in cultured hippocampal neurons. We show that Sema5B is proteolytically processed in neonatal brains and primary hippocampal cultures, resulting in the secretion of Sema5B fragments that include the biologically active semaphorin domain. Overexpression of full-length Sema5B in hippocampal neurons reduces synapse number while expression of a Sema5B construct lacking the semaphorin domain has no effect. Moreover, bath application with the proteolytically processed, secreted fragments containing the semaphorin domain of Sema5B, results in a rapid elimination of synaptic connections as demonstrated by time-lapse imaging. Conversely, depletion of endogenous Sema5B using RNA interference results in a significant increase in synapse number as well as a significant increase in the size of presynaptic and postsynaptic compartments.

Conclusion
Our results demonstrate that in addition to its role as a guidance cue, Sema5B regulates the development and maintenance of synapse size and number in hippocampal neurons. In addition, proteolytic cleavage of Sema5B results in the release of a potentially diffusible semaphorin domain that is a necessary component for its biological function in the regulation of synapse morphology.
Human NKT cells promote monocyte differentiation into suppressive myeloid antigen-presenting cells
Authors: Hegde Subramanya , Jankowska-Gan Ewa , Roenneburg Drew A , Torrealba Jose , Burlingham William J , Gumperz Jenny E 
Published: May 2009

Abstract
A novel pathway by which human NKT cells may promote T cell tolerance.
NKT cells have been shown to promote peripheral tolerance in a number of model systems, yet the processes by which they exert their regulatory effects remain poorly understood. Here, we show that soluble factors secreted by human NKT cells instruct human peripheral blood monocytes to differentiate into myeloid APCs that have suppressive properties. NKT-instructed monocytes acquired a cell surface phenotype resembling myeloid DCs. However, whereas control DCs that were generated by culturing monocytes with recombinant GM-CSF and IL-4 had a proinflammatory phenotype characterized by the production of IL-12 with little IL-10, NKT-instructed APCs showed the opposite cytokine production profile of high IL-10 with little or no IL-12. The control DCs efficiently stimulated peripheral blood T cell IFN-γ secretion and proliferation, whereas NKT-instructed APCs silenced these T cell responses. Exposure to NKT cell factors had a dominant effect on the functional properties of the DCs, since DCs differentiated by recombinant GM-CSF and IL-4 in the presence of NKT cell factors inhibited T cell responses. To confirm their noninflammatory effects, NKT-instructed APCs were tested in an in vivo assay that depends on the activation of antigen-specific human T cells. Control DCs promoted substantial tissue inflammation; however, despite a marked neutrophilic infiltrate, there was little edema in the presence of NKT-instructed APCs, suggesting the inflammatory cascade was held in check. These results point to a novel pathway initiated by NKT cells that can contribute to the regulation of human antigen-specific Th1 responses.
Characterization of the interaction between serum mannan-binding protein and nucleic acid ligands
Authors: Nakamura Natsuko , Nonaka Motohiro , Ma Bruce Yong , Matsumoto Shogo , Kawasaki Nobuko , Asano Shinji , Kawasaki Toshisuke 
Published: May 2009

Abstract
Serum C-type lectin MBP is shown to bind DNA and RNA from bacteria, plasmids, synthetic oligonucleotides, and fragmented DNA of apoptotic cells via its carbohydrate recognition domain.
Serum MBP, also known as MBL, is a C-type lectin that is known to be a soluble host defense factor involved in innate immunity. It has been well established that dying microbes and apoptotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display fragmented DNA on their surfaces. However, PRRs that mediate the recognition and clearance of free DNA and fragmented DNA in apoptotic cells have not been characterized clearly. Although MBP was reported recently to bind DNA as a novel ligand, binding characterization and the recognition implications have not been addressed yet. In this study, we show that MBP can bind DNA and RNA in a calcium-dependent manner from a variety of origins, including bacteria, plasmids, synthetic oligonucleotides, and fragmented DNA of apoptotic cells. Direct binding and competition studies indicate that MBP binds nucleic acids via its CRD to varying degrees and that MBP binds dsDNA more effectively than ssDNA and ssRNA. Furthermore, we reveal that the MBP-DNA complex does not trigger complement activation via the MBP lectin pathway, and the lectin pathway of complement activation is required for MBP-mediated enhancement of phagocytosis of targets bearing MBP ligands and that MBP can recognize the fragmented DNA presented on apoptotic cells. Therefore, we propose that the MBP lectin pathway may support effective recognition and clearance of cellular debris by facilitating phagocytosis, possibly through immunomodulatory mechanisms, thus preventing autoimmunity.
Measurements of laminar premixed methane—air flame thickness at ambient conditions
Authors: Clarke A , Hargrave G K 
Published: May 2009

A new experimental data set for the flame thickness of laminar premixed methane—air flames at ambient conditions is presented. Prior to combustion the temperature and pressure of the premixed mixture were 298 K>5 K and 100 kPa>5 kPa, respectively. The fuel—air equivalence ratio was varied from 0.8 to 1.4 in 0.05 steps. The data were obtained using simultaneous imaging of the visible and Schlieren cones on the central axis of the symmetrical flame front of a non-cooled burner configuration. The data were analysed and the plane obtained from the Schlieren image corrected using a one-dimensional energy balance to obtain the position of the cold surface of the flame and hence allow determination of the flame thickness. The data presented agree within experimental errors with the limited existing published data. For the range of equivalence ratios studied, a second-order equation was fitted and presented for methane—air flames at atmospheric pressure and ambient temperatures.
Modelling and simulation of thermal effects in wet clutches operating under boundary lubrication conditions
Authors: Marklund P , Sahlin F , Larsson R 
Published: May 2009

Wet clutches are frequently used in the drive trains of many modern vehicles. The behaviour of the clutches influences the behaviour of the whole drive train and therefore of the whole vehicle. The design of the clutch is very important because it operates in cooperation with the other parts of the drive train. The clutch also often has to work in the lubricant present in the transmission. To optimize the clutch for an application, properties such as disc geometry, materials, friction disc surface, and engagement axial force can be varied when designing the clutch. Today, the design process involves much testing, which is expensive and time consuming. There are no good hand-book solutions or engineering tools available, hence the designer has to be very experienced and often use trial and error methods in order to end up with a working clutch for an application. A simulation model is developed in this article, which in combination with a simple measurement technique for measuring the boundary lubrication friction coefficient is used to estimate temperature and torque transfer for a wet clutch working under limited slip conditions. The developed simulation model can be used as a design tool for wet clutches. The approach developed in this article can be used to investigate torque behaviour for wet clutches that have not been designed and is, therefore, suitable to use when optimizing the performance of a new clutch. The model includes fluid dynamics, contact mechanics, and temperature computations in the fluid film between the friction disc and the separator disc. Temperature computations in the clutch discs are also included in the model. The fluid dynamics calculations use homogenized flow factors to enable simulations of flow on a coarser grid and still include all surface roughness effects. The temperature distribution in the film in the sliding interface is approximated as a polynomial of the second order. The heat transfer in the grooves of the friction discs is solved by means of an equilibrium equation that includes radial cooling flow effects because of centrifugal flows. The temperature in the friction disc and separator disc is obtained from the solution of the full three-dimensional energy equation in polar cylindrical coordinates. The model is validated by measurements made in a test rig and good agreement between measurements and simulations is obtained, both with regard to temperature and transfered torque. The use of this model can reduce the time needed to develop a limited slip wet clutch application since the systematic way of finding the optimal clutch design will be more efficient than the often used Edisonian trial and error approach.
Association of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ2 with decreased basic metabolic rate in women with polycystic ovary syndrome
Authors: Koika Vasiliki , Marioli Dimitra J , Saltamavros Alexandros D , Vervita Vasiliki , Koufogiannis Kleanthis D , Adonakis George , Decavalas George , Georgopoulos Neoklis A 
Published: May 2009

ObjectiveThe peroxisome proliferator-activated receptor (PPAR)γ is a transcription factor involved in glucose homeostasis and energy metabolism. A missense mutation at codon 12 in the PPARγ2 has been associated with increased body mass index (BMI) and attenuated insulin resistance (IR) in polycystic ovary syndrome (PCOS). We have recently shown a decreased basic metabolic rate (BMR) in PCOS. The aim of the present study is to determine the prevalence of the Pro12Ala polymorphism of the PPARγ2 gene and its associations with indices of IR and BMR in lean and slightly overweight PCOS women.DesignCase–control association study involving 156 PCOS women with biochemical hyperandrogenism, chronic anovulation and polycystic ovarian morphology in ultrasound and 56 unrelated healthy controls.MethodsHormonal determinations were performed by electrochemiluminescence quantitation or RIA. BMR was measured by indirect calorimetry. All subjects were genotyped by a PCR–restriction fragment length polymorphism assay.ResultsGenotype frequencies of the Pro12Ala polymorphism in PPARγ2 did not differ among PCOS women and control subjects.The presence of Pro12Ala polymorphism of PPARγ2 was associated with lower BMR (P=0.04). This finding was valid in our subgroup of lean PCOS (BMI<25 kg/m2), in which the Ala variant was also associated with higher total testosterone values.ConclusionThe Pro12Ala polymorphism in the PPARγ2 gene is associated with decreased BMR in women with PCOS and biochemical hyperandrogenemia. These young women are therefore at risk to increase their body weight and should restrict their energy intake by diet and enhance their energy expenditure by exercise.