Role of S100 proteins in health and disease.

The S100 family of proteins contains 25 known members that share a high degree of sequence and structural similarity. However, only a limited number of family members have been characterized in depth, and the roles of other members are likely undervalued. Their importance should not be underestimated however, as S100 family members function to regulate a diverse array of cellular processes including proliferation, differentiation, inflammation, migration and/or invasion, apoptosis, Ca2+ homeostasis, and energy metabolism. Here we detail S100 target protein interactions that underpin the mechanistic basis to their function, and discuss potential intervention strategies targeting S100 proteins in both preclinical and clinical situations.

Type 2 diabetes - An autoinflammatory disease driven by metabolic stress.

Type 2 diabetes has traditionally been viewed as a metabolic disorder characterised by chronic high glucose levels, insulin resistance, and declining insulin secretion from the pancreas. Modern lifestyle, with abundant nutrient supply and reduced physical activity, has resulted in dramatic increases in the rates of obesity-associated disease conditions, including diabetes. The associated excess of nutrients induces a state of systemic low-grade chronic inflammation that results from production and secretion of inflammatory mediators from the expanded pool of activated adipocytes. Here, we review the mechanisms by which obesity induces adipose tissue dysregulation, detailing the roles of adipose tissue secreted factors and their action upon other cells and tissues central to glucose homeostasis and type 2 diabetes. Furthermore, given the emerging importance of adipokines, cytokines and chemokines in disease progression, we suggest that type 2 diabetes should now be viewed as an autoinflammatory disease, albeit one that is driven by metabolic dysregulation.

The Ras-related gene ERAS is involved in human and murine breast cancer.

Although Ras genes are frequently mutated in human tumors, these mutations are uncommon in breast cancer. However, many breast tumors show evidences of Ras pathway activation. In this manuscript, we have analyzed and characterized mouse mammary tumors generated by random Sleeping Beauty transposon mutagenesis and identify ERAS -a member of the RAS family silenced in adult tissues- as a new gene involved in progression and malignancy of breast cancer. Forced expression of ERAS in human non-transformed mammary gland cells induces a process of epithelial-to-mesenchymal transition and an increase in stem cells markers; these changes are mediated by miR-200c downregulation. ERAS expression in human tumorigenic mammary cells leads to the generation of larger and less differentiated tumors in xenotransplant experiments. Immunohistochemical, RT-qPCR and bioinformatics analysis of human samples show that ERAS is aberrantly expressed in 8-10% of breast tumors and this expression is associated with distant metastasis and reduced metastasis-free survival. In summary, our results reveal that inappropriate activation of ERAS may be important in the development of a subset of breast tumors. These findings open the possibility of new specific treatments for this subset of ERAS-expressing tumors.

Evaluating learning and attitudes on tissue engineering: a study of children viewing animated digital dome shows detailing the biomedicine of tissue engineering.

Informal science education creates opportunities for the general public to learn about complex health and science topics. Tissue engineering is a fast-growing field of medical science that combines advanced chemistries to create synthetic scaffolds, stem cells, and growth factors that individually or in combination can support the bodies own healing powers to remedy a range of maladies. Health literacy about this topic is increasingly important as our population ages and as treatments become more technologically advanced. We are using a science center planetarium as a projection space to engage and educate the public about the science and biomedical research that supports tissue engineering. The purpose of this study was to test the effectiveness of the films that we have produced for part of the science center planetarium demographic, specifically children ranging in age from 7 to 16 years. A two-group pre- and post-test design was used to compare children's learning and attitude changes in response to the two versions of the film. One version uses traditional voice-over narration; the other version uses dialog between two animated characters. The results of this study indicate that children demonstrated increases in knowledge of the topic with either film format, but preferred the animated character version. The percentage change in children's scores on the knowledge questions given before and after viewing the show exhibited an improvement from 23% correct to 61% correct on average. In addition, many of the things that the children reported liking were part of the design process of the art-science collaboration. Other results indicated that before viewing the shows 77% of the children had not even heard about tissue engineering and only 17% indicated that they were very interested in it, whereas after viewing the shows, 95% indicated that tissue engineering was a good idea. We also find that after viewing the show, 71% of the children reported that the show made them think, 75% enjoyed it, and 89% felt that they learned something. We discuss the potential impact the films might have on public knowledge, health literacy, and attitudes toward the science of tissue engineering.