Students with dyslexia: research projects at Northumbria University

Northumbria University has about 700 registered disabled students, the majority of whom (around 58 per cent) are registered as having dyslexia and account for approximately two per cent of the total student population. Therefore dyslexic students represent the largest single group of disabled students and are those with whom most staff are likely to come into contact. The research authors were keen to ascertain whether there was a difference in academic performance between dyslexic and non-dyslexic students in respect of degree classification and assignment marks and to investigate whether dyslexic students generally felt supported in their academic studies. Research involved both qualitative and quantitative strands and the areas explored include pre expectations; general support throughout study; methods, flexibility and clarity of learning tasks, in particular assessment and levels of performance throughout and at the end of their study. This research is ongoing, however, findings have proved invaluable as a basis in the construction of good practice guidelines in dealing with the pedagogic needs of this diverse student grou

Cyclic Phosphatidic Acid Inhibits Alkyl-Glycerophosphate-Induced Downregulation of Histone Deacetylase 2 Expression and Suppresses the Inflammatory Response in Human Coronary Artery Endothelial Cells

Activation of the endothelium by alkyl-glycerophosphate (AGP) has been implicated in the development of atherosclerosis. Our previous study suggested that cyclic phosphatidic acid (cPA) inhibits arterial wall remodeling in a rat model in vivo. However, the mechanisms through which specific target genes are regulated during this process remain unclear. Here, we examined whether cPA inhibited AGP-induced expression of class I histone deacetylases (HDACs, namely HDAC1, HDAC2, HDAC3, and HDAC8), which may affect subsequent transcriptional activity of target genes. Our experimental results showed that human coronary artery endothelial cells (HCAECs) expressed high levels of HDAC2 and low levels HDAC1, HDAC3, and HDAC8. Moreover, AGP treatment induced downregulation of HDAC2 expression in HCAECs. However, cotreatment with cPA inhibited this downregulation of HDAC2 expression. Interestingly, treatment with AGP increased the expression and secretion of endogenous interleukin (IL)-6 and IL-8; however, this effect was inhibited when HCAECs were cotreated with cPA or the synthetic peroxisome proliferator-activator receptor gamma (PPARγ) antagonist T0070907. Thus, our data suggested that cPA may have beneficial effects in inflammation-related cardiovascular disease by controlling HDAC2 regulation.ArticleInt. J. Med. Sci. 11(9):955-961 (2014)journal articl

Cyclic phosphatidic acid induces G0/G1 arrest, inhibits Akt phosphorylation, and downregulates cyclin D1 expression in colorectal cancer cells

17 Dec 2014. [Epub ahead of print]Lysophosphatidic acid (LPA) and its analogs are well-known mitogens for various cell types. Many reports have confirmed that several types of cancer cell produce LPA to promote survival, growth and tumorigenesis. This indicates that the interface between the LPA signaling pathway and the cell cycle signaling system is critical to the control of cancer cell proliferation. However, our previous study indicated that cyclic phosphatidic acid (cPA), which is structurally similar to LPA, inhibits the proliferation and migration of colon cancer cells. It has been reported that cPA shows several biological activities not shown by LPA. However, understanding of the detailed molecular and cellular mechanism underlying the regulation of the cell cycle by cPA is still in its infancy. In this study, we investigated the effect of cPA treatment on human DLD-1 colon cancer cells by analyzing cell cycle dynamics, gene expression, and AKT phosphorylation. Our findings indicate that cPA inhibits cell cycle progression in DLD-1 colon cancer cells via the downregulation of cyclin D1 and the inhibition of AKT phosphorylation.ArticleCellular Molecular Biology Letters. (17 Dec 2014) doi:10.1038/leu.2014.239journal articl

Lysophosphatidic acid signaling regulates the KLF9-PPAR gamma axis in human induced pluripotent stem cell-derived neurons

Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPAR gamma), a ligand-activated nuclear receptor, as well as its cognate receptor LPA(1) on human iPSC-derived neurons to enhance proliferation and neurite outgrowth. Furthermore, we found that the gene expression of Kruppel-like factor 9 (KLF9), a member of the large KLF transcription factor family, was induced by LPA treatment. Knockdown of KLF9 decreased proliferation and neurite outgrowth in vehicle- and LPA-treated IPSC-derived neurons compared to cells expressing KLF9. In conclusion, LPA plays dual roles as a ligand mediator through the activation of cell surface G-coupled protein receptors and as an intracellular second messenger through the activation of PPAR gamma. We discuss the contribution of the LPA(1)-PPAR(gamma)-KLF9 axis to neurite outgrowth and proliferation in human iPSC-derived neurons. (C) 2017 Elsevier Inc. All rights reserved.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 491(1):223-227 (2017)journal articl

The AGP-PPAR gamma axis promotes oxidative stress and diabetic endothelial cell dysfunction

Alkyl-glycerophosphate (AGP) accumulates in atherogenic oxidized-LDL and human atherosclerotic plaques and is a potent agonist of peroxisome-proliferator-activated receptor-gamma (PPAR gamma). Recent studies suggest a potential regulatory role for PPAR gamma in endothelial nitric oxide synthase (eNOS) expression/activation and nitrogen oxide (NO) generation in the vascular endothelium. Importantly, eNOS-induced NO and advanced glycation end-products (AGEs) are involved in blood-vessel damage, and diabetic patients exhibit high serum NO and AGE levels; however, the effect of AGP on NO- and AGE-mediated endothelium dysfunction remains unknown. Investigation of the AGP-specific effects on NO- and AGE-mediated dysfunction and the underlying molecular mechanisms revealed that AGP upregulated eNOS expression and NO production, and that eNOS silencing and gamma antagonism inhibited AGP-mediated eNOS upregulation and NO production. Moreover, AGP-PPAR gamma-axis-mediated NO production promoted the generation of reactive oxygen species and AGE formation. These results suggested that AGP plays a significant role in the initiation/progression of diabetes-related atherosclerosis through PPAR gamma activation. (C) 2018 Elsevier B.V. All rights reserved.ArticleMOLECULAR AND CELLULAR ENDOCRINOLOGY. 473:100-113 (2018)journal articl