71 research outputs found
Corporate Social Responsibility in European Sport Clubs: Analysis and Classification of Activities/Programs
Aim of paper and research questions: This study seeks to understand Corporate Social Responsibility (CSR) in European sport clubs by analysing and classifying the CSR activities and programs. Specifically, the study had two objectives: (1) To conduct a web-based analysis of documents, articles, and reports of the European sport clubs that already have CSR programs in place and (2) To determine the attributes and the type of those CSR programs
The Ser82 RAGE variant affects lung function and serum RAGE in smokers and sRAGE production in vitro
Introduction:
Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model.
Methods:
Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified.
Results:
Immunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production.
Conclusions:
This study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying COPD particularly for carriers of this AGER polymorphism
S100A14 Stimulates Cell Proliferation and Induces Cell Apoptosis at Different Concentrations via Receptor for Advanced Glycation End Products (RAGE)
S100A14 is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effects on different types of cells. However, exact extracellular roles of S100A14 have not been clarified yet. Here we investigated the effects of S100A14 on esophageal squamous cell carcinoma (ESCC) cell lines. Results demonstrated that low doses of extracellular S100A14 stimulate cell proliferation and promote survival in KYSE180 cells through activating ERK1/2 MAPK and NF-κB signaling pathways. Immunoprecipitation assay showed that S100A14 binds to receptor for advanced glycation end products (RAGE) in KYSE180 cells. Inhibition of RAGE signaling by different approaches including siRNA for RAGE, overexpression of a dominant-negative RAGE construct or a RAGE antagonist peptide (AmphP) significantly blocked S100A14-induced effects, suggesting that S100A14 acts via RAGE ligation. Furthermore, mutation of the N-EF hand of S100A14 (E39A, E45A) virtually reduced 10 µg/ml S100A14-induced cell proliferation and ERK1/2 activation. However, high dose (80 µg/ml) of S100A14 causes apoptosis via the mitochondrial pathway with activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase. High dose S100A14 induces cell apoptosis is partially in a RAGE-dependent manner. This is the first study to demonstrate that S100A14 binds to RAGE and stimulates RAGE-dependent signaling cascades, promoting cell proliferation or triggering cell apoptosis at different doses
Stakeholder communication in 140 characters or less: a study of community sport foundations
Community sport foundations (CSFs), like other non-profit organizations, are increasingly employing social media such as Twitter to communicate their mission and activities to their diverse stakeholder groups. However, the way these CSFs utilize social media for communicating such practices remains unclear. Through a mixed-method approach of content analysis of tweets from 22 CSFs established by English professional football clubs and interviews with key individuals within these CSFs (n = 7), this study examines the extent to which CSFs’ core activities are being communicated through Twitter and identifies the strategies employed for doing so. Reflecting the target audiences CSFs are seeking to reach through Twitter and the challenges associated with communication about projects involving marginalized groups, tweets largely concern programs related to sports participation and education. The most frequently employed communication strategy is to inform, rather than interact or engage with stakeholders. However, CSFs with higher organizational capacity attempt to go beyond mere informing towards engaging with stakeholder groups that relate to their social agenda, highlighting the importance of trained and dedicated social media personnel in optimizing CSFs’ use of Twitter for communication
The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity
The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks and are also able to exert disparate functions when released into the extracellular space. The emergent consequence for both inflammation and wound healing of the abnormal extracellular persistence of these factors may underlie many clinical disorders. DAMPs/PAMPs are recognized by hereditable receptors including the Toll-like receptors, the NOD1-like receptors and retinoic-acid-inducible gene I-like receptors, as well as the receptor for advanced glycation end products. These host molecules 'sense' not only pathogens but also misfolded/glycated proteins or exposed hydrophobic portions of molecules, activating intracellular cascades that lead to an inflammatory response. Equally important are means to not only respond to these molecules but also to eradicate them. We have speculated that their destruction through oxidative mechanisms normally exerted by myeloid cells, such as neutrophils and eosinophils, or their persistence in the setting of pathologic extracellular reducing environments, maintained by exuberant necrotic cell death and/or oxidoreductases, represent important molecular means enabling chronic inflammatory states
Imaging Mass Spectrometry of Diversified Cardiolipin Molecular Species in the Brain
MALDI imaging mass spectrometry (MALDI-IMS)
has been used successfully
in mapping different lipids in tissue sections, yet existing protocols
fail to detect the diverse species of mitochondria-unique cardiolipins
(CLs) in the brain which are essential for cellular and mitochondrial
physiology. We have developed methods enabling the imaging of individual
CLs in brain tissue. This was achieved by eliminating ion suppressive
effects by (i) cross-linking carboxyl/amino containing molecules on
tissue with 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride
and (ii) removing highly abundant phosphatidylcholine head groups
via phospholipase C treatment. These treatments allowed the detection
of CL species at 100 μm resolution and did not affect the amount
or molecular species distribution of brain tissue CLs. When combined
with augmented matrix application, these modifications allowed the
visualization and mapping of multiple CL species in various regions
of the brain including the thalamus, hippocampus, and cortex. Areas
such as the dentate and stratum radiatum exhibited higher CL signals
than other areas within the hippocampal formation. The habenular nuclear
(Hb)/dorsal third ventricle (D3 V) and lateral ventricle (LV) areas
were identified as CL “hot spots”. Our method also allowed
structural MS/MS fragmentation and mapping of CLs with identified
fatty acid residues and demonstrated a nonrandom distribution of individual
oxidizable (polyunsaturated fatty acid containing) and nonoxidizable
(nonpolyunsaturated containing) CLs in different anatomical areas
of the brain. To our knowledge, this method is the first label-free
approach for molecular mapping of diversified CLs in brain tissue
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