Author : Edward A. Dennis,Ralph A. This title covers disease states such as lymphoid leukemia, breast cancer, pulmonary fibrosis, systemic sclerosis, andinflammatory bowel disease, along with up-to-date research on signaling systems and mutations in transcription factors that provide new targets for treating disease. Articles written and edited by experts in the field Thematic volume covering disease states such as lymphoid leukemia, breast cancer, pulmonary fibrosis, systemic sclerosis, and inflammatory bowel disease Up-to-date research on signaling systems and mutations in transcription factors that provide new targets for treating disease.
Author : N. The editors have built Sulfoxides—Advances in Research and Application: Edition on the vast information databases of ScholarlyNews. You now have a source you can cite with authority, confidence, and credibility. Author : Ralph A. Each chapter gives a unique perspective on a different nutritional or dietary component or group of components, and reveals novel mechanisms by which dietary factors modulate the epigenome and affect development processes, chronic disease, and the aging process.
This pivotal text: Documents the epigenetic effect of antioxidants and their health benefits Adds to the understanding of mechanisms leading to disease susceptibility and healthy aging Illustrates that the epigenetic origins of disease occur in early fetal development Synthesizes the data regarding nutrient and epigenomic interactions Nutrition and Epigenetics highlights the interactions among nutrients, epigenetics, and health, providing an essential resource for scientists and clinical researchers interested in nutrition, aging, and metabolic diseases.
Bioactive food components like Brassica-derived 3,3'-diindolylmethane DIM are a promising area of study for cancer prevention and treatment. Due to its efficacy, availability, low cost, and low toxicity, DIM is currently in use as a treatment for recurrent respiratory papillomatosis and is in clinical trials for the prevention and treatment of prostate and cervical cancers.
DIM's anticancer activities include induction of cell cycle arrest and apoptosis, inhibition of angiogenesis, and immune activation.
Though some mechanisms for these activities in various cancer cells have been uncovered, it is clear that DIM works through multiple pathways. More research is necessary to determine the full extent of DIM's effects and to identify specific cellular targets of DIM.
Akt signaling is frequently dysregulated in breast cancer. Although it has been reported that DIM inhibits Akt signaling in breast cancer cells, the mechanism s for this action, as well as the kinetics and effects of lower, physiologically relevant concentrations of DIM, have remained unknown. In chapter 2 we demonstrate that physiologically relevant concentrations of DIM inhibit short- and long-term activation of Akt in the highly invasive MDA-MB breast cancer cells. In addition, DIM inhibits cell cycle progression and in vitro metastasis and induced apoptosis, which are all consistent with Akt inhibition.
The roles of specific upstream activators of the Akt pathway, including c-Met, in this activity have not been investigated. DIM also exerts some of its anti-cancer effects by activating the p38 pathway. DIM activates p38 in various cancer cells, including breast cancer cells, and that p38 activation as well as regulation of expression of various genes have been shown to play a role in DIM's effects in breast cancer cells.
However, the connection between these two effects has not been reported. We also show that DIM activates p38 under physiologically relevant conditions and this activation is partly responsible for DIM-induced up regulation of several genes and for DIM's induction of apoptosis. The results of the gene expression profiling study also provide many opportunities for follow up experiments. Their dietary and nutritional significance lies in their antioxidant properties and a number of investigators are looking at other health benefits of the compounds.
This volume surveys the current state of play in these and other areas of interest, including chemistry and biochemistry, immunology and cellular homeostasis. Chapters look in depth at some of the functions and effects in the body particularly with regard to exercise and fatigue, wound healing, cancer treatment and age-related diseases.
Providing an up to date, interdisciplinary approach, this book is of great interest to researchers and professionals in chemistry, food science, nutrition, biochemistry, health sciences and sports sciences. The 4-volume Encyclopedia of Human Nutrition, Third Edition, is a thorough revision of the previous award-winning version and reflects the scientific advances in the field of human nutrition. It presents the latest understanding on a wide range of nutrition-related topics including food safety, weight management, vitamins, bioengineering of foods, plant based diet and raw foods among others.
New articles on organic food, biofortification, nutritional labeling and the effect of religious customs on diet, among many others, reflect the dedication to currency in this revision. The most extensively studied of these, EGF Because the effects of AG are reversible, washing receptors EGFRs , are internalized on clathrin-coated sets up a condition whereby endosome-associated recep- vesicles CCVs and sorted either to late endosomes and tors that remain ligated with EGF become active.
Using lysosomes for degradation or to recycling compartments, this method, Wang et al. Thus, before internalization, activated as survival and differentiation. Moreover, increased levels of activated Ras were detected on these CCVs.
Several methods have been used to demonstrate that internalized EGFRs remain activated i. Therefore, similar to epithelial cells and fibro- fluorescent streptavidin and fluorescent antibodies to blasts, in PC12 cells Ras signaling is likely to proceed www. When The molecular machinery that directs internalization of MP1 was mislocalized from late endosomes by interfer- PTKRs might influence endosomal signaling. Interestingly, mislocalization extensively reviewed [27]. Thus, Ras signaling on late come from studies on intersectin, an adaptor protein endosomes requires the formation of a specific signaling containing multiple Src homology 3 SH3 domains that module that promotes the spatio-temporal regulation of associates with endocytic components, including epsin, Ras and MAPK activation.
Overexpression of intersectin transformed murine fibroblasts and stimu- Ras signaling on Golgi and the endoplasmic lated the c-Jun amino-terminal kinase JNK pathway reticulum and Elk-1 promoter activation [28].
The growth-stimu- Because endosomes are derived from the PM, such that latory effects of intersection might be mediated by Ras. In contrast, signaling on other endo- unpublished data. Because intersectin also interacts membrane compartments is somewhat counterintuitive. We used a novel in vivo probe Accordingly, recent work has focused on understanding for activated Ras, consisting of the RBD of Raf-1 fused to how scaffold proteins recruit components of MAPK cas- GFP, to show in living cells that activation of intracellular cades to specific subcellular compartments.
Twenty-four hours after transfection, the cells were serum-starved overnight to minimize Ras activation and then stimulated with EGF.
Current Opinion in Cell Biology , — www. Although there was mined. This observation suggests that branes. Like Ras, these pro- PC12 cell differentiation [32] may emanate from Golgi. Rap1 was M Philips, unpublished data. This pathway appears to be originally identified on the basis of its ability to reverse the predominant one in T cells that express relatively K-Ras-mediated transformation of murine fibroblasts by large amounts of RasGRP1.
Indeed, N-Ras was activated competing for Ras effectors [34]. However, recent evi- downstream of the T cell receptor in Jurkat cells exclu- dence indicates that Rap1 functions independently from sively on Golgi I Perez de Castro, T Bivona, M Philips Ras in the regulation of integrin-mediated adhesion [35]. Using a chimeric FRET CAPRI calcium-promoted Ras inactivator was active probe, Raichu—Rap, to monitor in living cells the sites specifically at the PM, allowing for simultaneous activa- of Rap1 activation, a recent report showed that Rap1 was tion of Ras on Golgi and inactivation on the PM mediated activated in response to growth factors primarily on intra- by a single intracellular second messenger.
However, Raichu—Rap was tar- myces cerevisiae, a novel inhibitor of Ras signaling, geted to membranes with the hypervariable region of ER-associated Ras inhibitor 1 ERI1 , has been identified K-Ras4B that directs proteins exclusively to the PM [5,6], and found to be expressed exclusively on ER D Levin, raising the question of how vesicular signaling was personal communication.
Thus, distinct modes of activa- detected. One explanation is that the relevant Rap1 tion and deactivation regulate Ras on different subcellular GEFs might be highly expressed on vesicles along with compartments. At may also occur on PM.
How- T Bivona and M Philips, unpublished data. Ras-independent ERK activation also takes place on the cytoplasmic face of endosomes because the MEK1 scaffold MP1 is recruited to this compartment by the p14 adaptor protein.
Src participates in the activation of PLCg. These membrane compartment. Understanding how interactions between receptors and intracellular signaling molecules such as adaptors, Elucidating the biological roles for PTKR-induced endo- GTPases and kinases are regulated in intact cells will membrane signaling will require multiple methodologies, undoubtedly provide insight into the ways that cells sense including validation in transgenic animals.
The endo- and adapt to environmental cues. Recent advances in cell membrane system constitutes the most extensive mem- biology have ushered in a new age for the study of old brane platform present in eukaryotic cells.
Moreover, signaling pathways, whose spatio-temporal dynamics can compartmentalization of signaling events allows for a Current Opinion in Cell Biology , — www. Science , limited number of signaling molecules functioning in only
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