bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a large scale integrated map of macrophage pathogen recognition and effector systems
Authors: Raza Sobia , McDerment Neil , Lacaze Paul A , Robertson Kevin , Watterson Steven , Chen Ying , Chisholm Michael , Eleftheriadis George , Monk Stephanie , O'Sullivan Maire , Turnbull Arran , Roy Douglas , Theocharidis Athanasios , Ghazal Peter , Freeman Tom C 
Published: May 2010

AbstractBackgroundIn an effort to better understand the molecular networks that underpin macrophage activation we have been assembling a map of relevant pathways. Manual curation of the published literature was carried out in order to define the components of these pathways and the interactions between them. This information has been assembled into a large integrated directional network and represented graphically using the modified Edinburgh Pathway Notation (mEPN) scheme.ResultsThe diagram includes detailed views of the toll-like receptor (TLR) pathways, other pathogen recognition systems, NF-kappa-B, apoptosis, interferon signalling, MAP-kinase cascades, MHC antigen presentation and proteasome assembly, as well as selected views of the transcriptional networks they regulate. The integrated pathway includes a total of 496 unique proteins, the complexes formed between them and the processes in which they are involved. This produces a network of 2,170 nodes connected by 2,553 edges.ConclusionsThe pathway diagram is a navigable visual aid for displaying a consensus view of the pathway information available for these systems. It is also a valuable resource for computational modelling and aid in the interpretation of functional genomics data. We envisage that this work will be of value to those interested in macrophage biology and also contribute to the ongoing Systems Biology community effort to develop a standard notation scheme for the graphical representation of biological pathways.
Generation of functional CD8+ T Cells by human dendritic cells expressing glypican-3 epitopes
Authors: O'Beirne James , Farzaneh Farzin , Harrison Phillip M 
Published: May 2010

Abstract

Background
Glypican 3 (GPC-3) is an oncofoetal protein that is expressed in most hepatocellular carcinomas (HCC). Since it is a potential target for T cell immunotherapy, we investigated the generation of functional, GPC-3 specific T cells from peripheral blood mononuclear cells (PBMC).

Methods
Dendritic cells (DC) were derived from adherent PBMC cultured at 37°C for 7 days in X-Vivo, 1% autologous plasma, and 800 u/ml GM-CSF plus 500 u/ml IL-4. Immature DC were transfected with 20 μg of in vitro synthesised GPC-3 mRNA by electroporation using the Easy-ject plus system (Equibio, UK) (300 V, 150 μF and 4 ms pulse time), or pulsed with peptide, and subsequently matured with lipopolysaccharide (LPS). Six predicted GPC-3 peptide epitopes were synthesized using standard f-moc technology and tested for their binding affinity to HLA-A2.1 molecules using the cell line T2.

Results
DC transfected with GPC-3 mRNA but not control DC demonstrated strong intracellular staining for GPC-3 and in vitro generated interferon-gamma expressing T cells from autologous PBMC harvested from normal subjects. One peptide, GPC-3522-530 FLAELAYDL, fulfilled our criteria as a naturally processed, HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitope: i) it showed high affinity binding to HLA-A2, in T2 cell binding assay; ii) it was generated by the MHC class I processing pathway in DC transfected with GPC-3 mRNA, and iii) HLA-A2 positive DC loaded with the peptide stimulated proliferation in autologous T cells and generated CTL that lysed HLA-A2 and GPC-3 positive target cells.

Conclusions
These findings demonstrate that electroporation of GPC-3 mRNA is an efficient method to load human monocyte-derived DC with antigen because in vitro they generated GPC-3-reactive T cells that were functional, as shown by interferon-gamma production. Furthermore, this study identified a novel naturally processed, HLA-A2-restricted CTL epitope, GPC-3522-530 FLAELAYDL, which can be used to monitor HLA-A2-restricted CTL responses in patients with HCC. Further studies are required to investigate whether anti-GPC-3 immunotherapy has a role in the treatment of GPC-3 dependent tumours, such as HCC.
Inhibitor of IκB kinase activity, BAY 11-7082, interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells
Authors: Miyamoto Rie , Ito Tomoki , Nomura Shosaku , Amakawa Ryuichi , Amuro Hideki , Katashiba Yuichi , Ogata Makoto , Murakami Naoko , Shimamoto Keiko , Yamazaki Chihiro , Hoshino Katsuaki , Kaisho Tsuneyasu , Fukuhara Shirou 
Published: May 2010

Abstract
Introduction
Plasmacytoid dendritic cells (pDCs) play not only a central role in the antiviral immune response in innate host defense, but also a pathogenic role in the development of the autoimmune process by their ability to produce robust amounts of type I interferons (IFNs), through sensing nucleic acids by toll-like receptor (TLR) 7 and 9. Thus, control of dysregulated pDC activation and type I IFN production provide an alternative treatment strategy for autoimmune diseases in which type I IFNs are elevated, such as systemic lupus erythematosus (SLE). Here we focused on IκB kinase inhibitor BAY 11-7082 (BAY11) and investigated its immunomodulatory effects in targeting the IFN response on pDCs.

Methods
We isolated human blood pDCs by flow cytometry and examined the function of BAY11 on pDCs in response to TLR ligands, with regards to pDC activation, such as IFN-α production and nuclear translocation of interferon regulatory factor 7 (IRF7) in vitro. Additionally, we cultured healthy peripheral blood mononuclear cells (PBMCs) with serum from SLE patients in the presence or absence of BAY11, and then examined the inhibitory function of BAY11 on SLE serum-induced IFN-α production. We also examined its inhibitory effect in vivo using mice pretreated with BAY11 intraperitonealy, followed by intravenous injection of TLR7 ligand poly U.

Results
Here we identified that BAY11 has the ability to inhibit nuclear translocation of IRF7 and IFN-α production in human pDCs. BAY11, although showing the ability to also interfere with tumor necrosis factor (TNF)-α production, more strongly inhibited IFN-α production than TNF-α production by pDCs, in response to TLR ligands. We also found that BAY11 inhibited both in vitro IFN-α production by human PBMCs induced by the SLE serum and the in vivo serum IFN-α level induced by injecting mice with poly U.

Conclusions
These findings suggest that BAY11 has the therapeutic potential to attenuate the IFN environment by regulating pDC function and provide a novel foundation for the development of an effective immunotherapeutic strategy against autoimmune disorders such as SLE.
Individual and occupational risk factors for knee osteoarthritis: results of a case-control study in Germany
Authors: Klussmann André , Gebhardt Hansjürgen , Nübling Matthias , Liebers Falk , Quirós Perea Emilio , Cordier Wolfgang , von Engelhardt Lars V , Schubert Markus , Dávid Andreas , Bouillon Bertil , Rieger Monika A 
Published: May 2010

Abstract
Introduction
A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The distinction between work-related and other factors is crucial in assessing the risk and in deriving preventive measures in occupational health.

Methods
In a case-control study, patients with and without symptomatic knee osteoarthritis (OA) were questioned by means of a standardised questionnaire complemented by a semi-standardised interview. Controls were matched and assigned to the cases by gender and age. Conditional logistic regression was used in analysing data.

Results
In total, 739 cases and 571 controls were included in the study. In women and men, several individual and occupational predictors for knee OA could be described: obesity (odds ratio (OR) up to 17.65 in women and up to 12.56 in men); kneeling/squatting (women, OR 2.52 (>8,934 hours/life); men, 2.16 (574 to 12,244 hours/life), 2.47 (>12,244 hours/life)); genetic predisposition (women, OR 2.17; men, OR 2.37); and sports with a risk of unapparent trauma (women, OR 2.47 (≥1,440 hours/life); men, 2.58 (≥3,232 hours/life)). In women, malalignment of the knee (OR 11.54), pain in the knee already in childhood (OR 2.08), and the daily lifting and carrying of loads (≥1,088 tons/life, OR 2.13) were related to an increased OR; sitting and smoking led to a reduced OR.

Conclusions
The results support a dose-response relationship between kneeling/squatting and symptomatic knee OA in men and, for the first time, in women. The results concerning general and occupational predictors for knee OA reflect the findings from the literature quite well. Yet occupational risks such as jumping or climbing stairs/ladders, as discussed in the literature, did not correlate with symptomatic knee OA in the present study. With regards to occupational health, prevention measures should focus on the reduction of kneeling activities and the lifting and carrying of loads as well as general risk factors, most notably the reduction of obesity. More intervention studies of the effectiveness of tools and working methods for reducing knee straining activities are needed.
Low hemoglobin is associated with poor functional outcome after non-traumatic, supratentorial intracerebral hemorrhage
Authors: Diedler Jennifer , Sykora Marek , Hahn Philipp , Heerlein Kristin , Schölzke Marion N , Kellert Lars , Bösel Julian , Poli Sven , Steiner Thorsten 
Published: May 2010

Abstract
Introduction
The impact of anemia on functional outcome and mortality in patients suffering from non-traumatic intracerebral hemorrhage (ICH) has not been investigated. Here, we assessed the relationship between hemoglobin (HB) levels and clinical outcome after ICH.

Methods
One hundred and ninety six patients suffering from supratentorial, non-traumatic ICH were extracted from our local stroke database (June 2004 to June 2006). Clinical and radiologic computed tomography data, HB levels on admission, mean HB values and nadir during hospital stay were recorded. Outcome was assessed at discharge and 3 months using the modified Rankin score (mRS).

Results
Forty six (23.5%) patients achieved a favorable functional outcome (mRS ≤ 3) and 150 (76.5%) had poor outcome (mRS 4 - 6) at discharge. Patients with poor functional outcome had a lower mean HB (12.3 versus 13.7 g/dl, P < 0.001) and nadir HB (11.5 versus 13.0 g/dl, P < 0.001). Ten patients (5.1%) received red blood cell (RBC) transfusions. In a multivariate logistic regression model, the mean HB was an independent predictor for poor functional outcome at three months (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.92, P = 0.007), along with National Institute of Health Stroke Scale (NIHSS) at admission (OR 1.17, 95% CI 1.11 - 1.24, P < 0.001), and age (OR 1.08, 95% CI 1.04 - 1.12, P < 0.001).

Conclusions
We report an association between low HB and poor outcome in patients with non-traumatic, supratentorial ICH. While a causal relationship could not be proven, previous experimental studies and studies in brain injured patients provide evidence for detrimental effects of anemia on brain metabolism. However, the potential risk of anemia must be balanced against the risk of harm from red blood cell infusion.
The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction
Authors: Terrando Niccolò , Rei Fidalgo António , Vizcaychipi Marcela , Cibelli Mario , Ma Daqing , Monaco Claudia , Feldmann Marc , Maze Mervyn 
Published: May 2010

Abstract
Introduction
The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 (HMGB-1), microglial activation, and cognitive dysfunction. Disabling the interleukin (IL)-1 signaling pathway is sufficient to reduce inflammation and ameliorate the disability.

Methods
Endotoxemia was induced in wild-type and IL-1R-/- mice by intra peritoneal injection of E. Coli LPS (1 mg/kg). Markers of inflammation were assessed both peripherally and centrally, and correlated to behavioral outcome using trace fear conditioning.

Results
Increase in plasma tumor necrosis factor-α (TNFα) peaked at 30 minutes after LPS challenge. Up-regulation of IL-1β, IL-6 and HMGB-1 was more persistent, with detectable levels up to day three. A 15-fold increase in IL-6 and a 6.5-fold increase in IL-1β mRNA at 6 hours post intervention (P < 0.001 respectively) was found in the hippocampus. Reactive microgliosis was observed both at days one and three, and was associated with elevated HMGB-1 and impaired memory retention (P < 0.005). Preemptive administration of IL-1 receptor antagonist (IL-1Ra) significantly reduced plasma cytokines and hippocampal microgliosis and ameliorated cognitive dysfunction without affecting HMGB-1 levels. Similar results were observed in LPS-challenged mice lacking the IL-1 receptor to those seen in LPS-challenged wild type mice treated with IL-1Ra.

Conclusions
These data suggest that by blocking IL-1 signaling, the inflammatory cascade to LPS is attenuated, thereby reducing microglial activation and preventing the behavioral abnormality.
Optimal TLR9 signal converts tolerogenic CD4–8– DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses
Authors: Zhang Xueshu , Munegowda Manjunatha Ankathatti , Yuan Jinying , Wei Yi , Xiang Jim 
Published: May 2010

Abstract
Conversion of tolerogenic DCs into immunogenic ones by time-limited CpG signaling allows for stimulation of antitumor immunity via activation of CD4+ Th1/Th17 and NK cell responses.
Abstract
TLR ligands have been reported to promote DC maturation and enhance CD8+ CTL responses. We have demonstrated previously that CD4–8– DCs secreting TGF-β stimulate CD4+ Tr1 cell responses. Here, we have assessed whether TLR4 and TLR9 signaling through LPS and CpG stimulation can convert CD4−8− DC-induced tolerance. We demonstrate that immature OVA-pulsed CD4–8– DCs cultured in medium with LPS (2 μg/ml) and CpG (5 μg/ml) for 8 h became mature DCs (DCOVA) with no TGF-β secretion. CpG-treated, CD4–8– DCOVA-secreting IL-6/IL-15 induced IFN-γ/IL-17-secreting/T-bet- and ROR-γt-expressing CD4+ Th1/Th17, whereas LPS-treated CD4–8– DCOVA stimulated IFN-γ-secreting/T-bet-expressing CD4+ Th1 responses. The former also significantly stimulated more efficient OVA-specific CD8+ T cell responses and antitumor immunity against OVA-expressing BL6-10OVA tumor cells than the latter (P&lt;0.05). CpG-treated, CD4–8– DCOVA-stimulated CD4+ Th1/Th17 cell responses and antitumor immunity were found to be reduced by using neutralizing anti-IL-6, IL-15, and NK1.1 antibodies in wild-type C57BL/6 mice, IL-15R−/− mice for immunization, or CD4–8– (IL-6−/−) DCOVA for immunization in C57BL/6 mice. Interestingly, in vitro-generated CD4+ Th17 cells significantly enhanced LPS-treated, CD4–8– DCOVA-induced in vivo antitumor immunity via increasing CD8+ CTL responses (P&lt;0.05), although they did not show any direct killing activity against tumor cells in vitro. In addition, prolonged 48 h CpG-treated CD4–8– DCOVA dramatically diminished its cytokine secretion, stimulatory effect, and antitumor immunity. Taken together, our data demonstrate an effect of conversion of tolerogenic DCs into immunogenic ones capable of stimulating antitumor immunity via activating CD4+ Th1/Th17 and NK cell responses by optimal CpG signaling, which may advance current understanding of the importance of TLR9 signaling in a DC-based cancer vaccine.
A model of visual–olfactory integration for odour localisation in free-flying fruit flies
Authors: Stewart Finlay J. , Baker Dean A. , Webb Barbara 
Published: May 2010

SUMMARYFlying fruit flies (Drosophila melanogaster) locate a concealed appetitive odour source most accurately in environments containing vertical visual contrasts. To investigate how visuomotor and olfactory responses may be integrated, we examine the free-flight behaviour of flies in three visual conditions, with and without food odour present. While odour localisation is facilitated by uniformly distributed vertical contrast as compared with purely horizontal contrast, localised vertical contrast also facilitates odour localisation, but only if the odour source is situated close to it. We implement a model of visuomotor control consisting of three parallel subsystems: an optomotor response stabilising the model fly's yaw orientation; a collision avoidance system to saccade away from looming obstacles; and a speed regulation system. This model reproduces many of the behaviours we observe in flies, including visually mediated ‘rebound’ turns following saccades. Using recordings of real odour plumes, we simulate the presence of an odorant in the arena, and investigate ways in which the olfactory input could modulate visuomotor control. We reproduce the experimental results by using the change in odour intensity to regulate the sensitivity of collision avoidance, resulting in visually mediated chemokinesis. Additionally, it is necessary to amplify the optomotor response whenever odour is present, increasing the model fly's tendency to steer towards features of the visual environment. We conclude that visual and olfactory responses of Drosophila are not independent, but that relatively simple interaction between these modalities can account for the observed visual dependence of odour source localisation.
Homeostasis of glucose in the rainbow trout (Oncorhynchus mykissWalbaum): the role of serotonin
Authors: Tubío Rosa I. Caamaño , Pérez-Maceira Jorge , Aldegunde Manuel 
Published: May 2010

SUMMARYIn this study, we evaluated, for the first time, the 5-HT (serotonin)-mediated control of glucose homeostasis in the rainbow trout Oncorhynchus mykiss. Intraperitoneal administration of 5-HT increased plasma levels of glucose, adrenaline and noradrenaline. By contrast, intracerebroventricular administration of 5-HT did not cause any significant variation in plasma levels of glucose. The release of endogenous 5-HT following intraperitoneal administration of d-fenfluramine led to a significant increase in plasma levels of glucose and adrenaline. Intraperitoneal administration of (1) MIAN (a 5-HT2 receptor antagonist) did not block either the hyperglycaemic action or the increase in plasma levels of adrenaline induced by 5-HT, but did block the increase in plasma levels of noradrenaline, and (2) 5-CT (a 5-HT1 agonist) increased the plasma levels of glucose and of adrenaline, without altering those of noradrenaline. Administration of TFMPP (a 5-HT1B agonist) did not increase the plasma levels of glucose, and the hyperglycaemic action of 5-HT was not blocked by antagonists of 5-HT1A (WAY 100635), 5-HT1D (BRL 15572), 5-HT2B (SB 204741) or 5-HT7 (pimozide) receptors. It was demonstrated that, in rainbow trout, peripheral 5-HT, but not brain 5-HT intervenes in the modulation of glucose homeostasis with a hyperglycaemic effect. This effect is associated with the release of adrenaline and activation of 5-HT1-like receptors. As far as could be determined in the present study, these 5-HT1-like receptors are unrelated to either the 5-HT1A, 5-HT1B or 5-HT1D receptor subtypes of mammals. The 5-HT2-type receptors may mediate the release of noradrenaline, but not of adrenaline, and furthermore, do not appear to play an important role in the hyperglycaemic effect exerted by 5-HT.
Sustained performance by red and white muscle fibres from the dogfish Scyliorhinus canicula
Authors: Curtin N. A. , Lou F. , Woledge R. C. 
Published: May 2010

SUMMARY
The mechanical performance of red and white muscle fibres from dogfish was compared during a long series of contractions with sinusoidal movement or under isometric conditions at 12°C (normal in vivo temperature). Power output was measured during sinusoidal movement at 0.75 Hz and peak-to-peak amplitude about 12% L0. Tetanus duty cycle was 33% (0.44 s) at phase −8% (first stimulus at 0.107 s before shortening started). Initially, the red fibres produced only about one third as much power as the white fibres, 6.57±0.63 W kg−1 wet mass (mean ± s.e.m.) and 18.3±2.3, respectively. Red fibres were better at sustaining power output; it declined rapidly to about 60% of its initial value and then remained relatively steady for up to 450 cycles of movement. Force during shortening declined, but force during stretch did not increase: force always relaxed to a low value before stretch started. By contrast, net power output by white fibres declined rapidly to zero within about 50 cycles. Two changes contributed: decline in force during shortening and an increase in force during stretch because relaxation became progressively less complete during the series of contractions. In isometric series (0.44 s stimulation every 1.33 s, cycle frequency 0.75 Hz), red and white fibres sustained peak isometric force similarly; in the 50th cycle force was 59±3% and 56±4% of initial values. The time required for force to relax to 10% of its maximum value decreased during the series for red fibres and increased for white fibres.
Underwater attachment in current: the role of setose attachment structures on the gills of the mayfly larvaeEpeorus assimilis(Ephemeroptera, Heptageniidae)
Authors: Ditsche-Kuru P. , Koop J. H. E. , Gorb S. N. 
Published: May 2010

SUMMARYSetose pads of aquatic Epeorus assimilis larvae are specialised structures located ventrally on the part of the gill lamella contacting the substrate and were suggested to have an attachment function in strong currents. In order to test the role of these setose pads in underwater attachment for the first time, we measured friction (shear) forces generated by the gill lamellae on solid substrates. Moreover, the influence of a different kind of surface roughness on attachment was investigated. Scanning electron microscopy showed that four different seta types can be found on the pads. Our results revealed that the pads significantly contributed to friction force generated on smooth and on some rough substrates but not on certain surfaces of intermediate roughness. The contribution of pads to the friction coefficient in experiments was lower than expected under natural conditions, which may be caused by a smaller contact area between the pads and the substrate (changes in material properties, lack of the active control of body positioning of the larva). The friction coefficient of the gill lamellae with the substrate depended on the surface roughness of the substrate and on the pulling direction. These results suggest that interlocking between structures of the insect cuticle and substrate irregularities, as well as molecular adhesion, contribute to friction.