Heatmap of the genes in the module regulated by <i>SPAG5</i> in MBC.

<p>Red corresponds to up-regulation and green to down-regulation. The 66 MBC tumors are sorted according to their gene expression level of <i>SPAG5</i>.</p

Heatmap of the genes in the module regulated by <i>THY1</i> in MBC.

<p>Red corresponds to up-regulation and green to down-regulation. The 66 MBC tumors are sorted according to their gene expression level of <i>THY1</i>. </p

Flowchart outlining the steps in the CONEXIC analysis.

<p>Flowchart outlining the steps in the CONEXIC analysis.</p

Graphic output of the LitVAn result for the MBC <i>SPAG5</i> module and corresponding Kaplan-Meier survival analysis.

<p><b>A</b>) Significantly over-represented terms are represented as red circles and their association (graph edges) with multiple genes (yellow circles) from the module. The green dots represent the publication that significantly associates between the gene and the term, and the numbers in the green dots are the PubMed IDs for the respective publications. <b>B</b>) Distant metastasis free survival of the 66 MBC patients stratified by <i>SPAG5</i> gene expression. The numbers below the plots indicate the number of patients at risk in each group at the given time points.</p

The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells

<p>Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.</p

The 10 most significantly enriched biological processes in the malignant ovarian tumors in the study cohort [31].

<p>*FDR<0.05 and ≥3 recognized genes/biological function were required to consider a gene ontology (GO) process significant. 731 significant.</p><p>GO processes were identified.</p>a<p>Number of genes in the study cohort correlating to the GO process.</p>b<p>Number of genes in the GO process.</p><p>The 10 most significantly enriched biological processes in the malignant ovarian tumors in the study cohort <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Chen1" target="_blank">[31]</a>.</p

Clinicopathologic features of malignant and borderline ovarian tumors in the study cohort.

<p><i>Feature</i>: M = Malignant, Bo = Borderline; <i>Tissue type</i>: tissue used for RNA extraction, FT = Fallopian Tube, N/A = Unknown; <i>Survival</i>: Disease specific survival, Alive = alive at start of study; <i>C-signature</i>: corresponding ovarian molecular subtype <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Tothill1" target="_blank">[18]</a>; <i>BC subtype</i>: corresponding intrinsic breast cancer subtype <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Hu1" target="_blank">[22]</a>.</p><p>Clinicopathologic features of malignant and borderline ovarian tumors in the study cohort.</p

SAM analysis.

<p>Supervised hierarchical clustering of malignant (n = 37) and benign (n = 17) serous ovarian tumors (FDR <1%). Red represents relative upregulation and green represents relative downregulation.</p

Ovarian cancer subtypes.

<p>Serous ovarian tumors in the study cohort with corresponding ovarian cancer subtypes (“C-signatures”) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Tothill1" target="_blank">[18]</a>. The rows outline the tumor types with the representation in each subtype in percent within parentheses. The p-value is calculated using Fisher's exact test.</p><p>Ovarian cancer subtypes.</p

Correlations between ovarian and breast cancer molecular subtypes.

<p>Correlations between specific ovarian cancer C-signatures <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Tothill1" target="_blank">[18]</a> and the intrinsic breast cancer subtypes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107643#pone.0107643-Hu1" target="_blank">[22]</a> in the serous ovarian tumors in the study cohort. Tumors within each ovarian cancer C-signature are shown along the X axis, and the colored bars represent the percentage (on the Y axis) of each intrinsic breast cancer subtype within the respective C-signatures.</p