A Systems Approach Demonstrating Sphingolipid-Dependent Transcription in Stress Responses

Author(s):  
Alan J. Wilder ◽  
L. Ashley Cowart
Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5143
Author(s):  
Gary Hardiman ◽  
Stephen J. Savage ◽  
E. Starr Hazard ◽  
Willian A. da Silveira ◽  
Rebecca Morgan ◽  
...  

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.


2005 ◽  
Vol 33 (5) ◽  
pp. 1166-1169 ◽  
Author(s):  
L.A. Cowart ◽  
Y.A. Hannun

In addition to their crucial role in membrane structure in Saccharomyces cerevisiae, sphingolipids serve vital roles in various aspects of yeast biology including endocytosis, intracellular protein transport and stress responses. Although previous studies have unequivocally demonstrated the sphingolipid requirements for these processes, few studies have contributed mechanistic information. We have used a systems approach including microarray, lipidomics and metabolic modelling to better understand (i) biochemical relationships between various branches of sphingolipid metabolism and pathways and contributing pathways such as fatty acid metabolism and phospholipid synthesis, (ii) the changes in cellular sphingolipid composition under various conditions and (iii) the effects of these changes on the transcriptional profiles and subsequently, cell phenotypes. Thus far, these approaches have indicated roles for sphingolipids in major transcriptional changes in response to heat stress, carbon source utilization, sporulation, cell wall integrity and other basic cellular functions. Although the yeast genome is fully sequenced, nearly 50% of all transcribed open reading frames remain uncharacterized with regard to cellular function; therefore, a major advantage of this approach is the ability to identify both biochemical and biological roles for enzymes and their products within broad cellular contexts.


2008 ◽  
Vol 16 (3) ◽  
pp. 112-115 ◽  
Author(s):  
Stephan Bongard ◽  
Volker Hodapp ◽  
Sonja Rohrmann

Abstract. Our unit investigates the relationship of emotional processes (experience, expression, and coping), their physiological correlates and possible health outcomes. We study domain specific anger expression behavior and associated cardio-vascular loads and found e.g. that particularly an open anger expression at work is associated with greater blood pressure. Furthermore, we demonstrated that women may be predisposed for the development of certain mental disorders because of their higher disgust sensitivity. We also pointed out that the suppression of negative emotions leads to increased physiological stress responses which results in a higher risk for cardiovascular diseases. We could show that relaxation as well as music activity like singing in a choir causes increases in the local immune parameter immunoglobuline A. Finally, we are investigating connections between migrants’ strategy of acculturation and health and found e.g. elevated cardiovascular stress responses in migrants when they where highly adapted to the German culture.


2001 ◽  
Vol 6 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Lawrence A. Pervin

David Magnusson has been the most articulate spokesperson for a holistic, systems approach to personality. This paper considers three concepts relevant to a dynamic systems approach to personality: dynamics, systems, and levels. Some of the history of a dynamic view is traced, leading to an emphasis on the need for stressing the interplay among goals. Concepts such as multidetermination, equipotentiality, and equifinality are shown to be important aspects of a systems approach. Finally, attention is drawn to the question of levels of description, analysis, and explanation in a theory of personality. The importance of the issue is emphasized in relation to recent advances in our understanding of biological processes. Integrating such advances into a theory of personality while avoiding the danger of reductionism is a challenge for the future.


2006 ◽  
Vol 22 (4) ◽  
pp. 259-267 ◽  
Author(s):  
Eelco Olde ◽  
Rolf J. Kleber ◽  
Onno van der Hart ◽  
Victor J.M. Pop

Childbirth has been identified as a possible traumatic experience, leading to traumatic stress responses and even to the development of posttraumatic stress disorder (PTSD). The current study investigated the psychometric properties of the Dutch version of the Impact of Event Scale-Revised (IES-R) in a group of women who recently gave birth (N = 435). In addition, a comparison was made between the original IES and the IES-R. The scale showed high internal consistency (α = 0.88). Using confirmatory factor analysis no support was found for a three-factor structure of an intrusion, an avoidance, and a hyperarousal factor. Goodness of fit was only reasonable, even after fitting one intrusion item on the hyperarousal scale. The IES-R correlated significantly with scores on depression and anxiety self-rating scales, as well as with scores on a self-rating scale of posttraumatic stress disorder. Although the IES-R can be used for studying posttraumatic stress reactions in women who recently gave birth, the original IES proved to be a better instrument compared to the IES-R. It is concluded that adding the hyperarousal scale to the IES-R did not make the scale stronger.


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