Nonthermal electromagnetic fields: From first messenger to therapeutic applications

Nonthermal pulsed electromagnetic fields, from low frequency to pulse-modulated radio frequency, have been successfully employed as adjunctive therapy for the treatment of delayed and non-union fractures, fresh fractures and chronic wounds. Recent increased understanding of the mechanism of action of electromagnetic fields (EMF) has permitted technologic advances allowing the development of EMF devices which are portable and disposable, can be incorporated into dressings, supports and casts, and can be used over clothing. This broadens the use of non-pharmacological, non-invasive EMF therapy to the treatment of postoperative pain and edema to enhance surgical recovery. EMF therapy is rapidly becoming a standard part of surgical care, and new, more significant, clinical applications for osteoarthritis, brain and cardiac ischemia and traumatic brain injury are in the pipeline. This study reviews recent evidence which suggests that calmodulin (CaM)-dependent nitric oxide signaling is involved in cell and tissue response to weak nonthermal EMF signals. There is abundant evidence that EMF signals can be configured a priori to increase the rate of CaM activation, which, in turn, can modulate the biochemical cascades living cells and tissues employ in response to external insult. Successful applications in pilot clinical trials, coupled with evidence at the cellular and animal levels, provide support that EMF is a first messenger that can modulate the response of challenged biological systems.     

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

1. Download : Download high-res image (287KB)
2. Download : Download full-size image

     

The family of organo-phosphate transport proteins includes a transmembrane regulatory protein

This review article briefly summarizes aspects of our current understanding of the Uhp sugar phosphate transport system in enteric bacteria, particularly the mode of genetic regulation of its synthesis. This regulation occurs by a process that involves an example of the very widespread and ever-growing group of so-called two-component bacterial regulatory systems, a mechanism of response to environmental signals that employs phosphate transfer reactions between constituent proteins. Of emphasis here is the unusual involvement in transmembrane signaling of the UhpC protein which is related in sequence and structure to some transport proteins, including the very protein whose synthesis it helps regulate.     

The role of FGF signaling in guiding coordinate movement of cell groups: Guidance cue and cell adhesion regulator?

Cell migration influences cell-cell interactions to drive cell differentiation and organogenesis. To support proper development, cell migration must be regulated both temporally and spatially. Mesoderm cell migration in the Drosophila embryo serves as an excellent model system to study how cell migration is controlled and influences organogenesis. First, mesoderm spreading transforms the embryo into a multilayered form during gastrulation and, subsequently, cells originating from the caudal visceral mesoderm (CVM) migrate along the entire length of the gut. Here we review our studies, which have focused on the role of fibroblast growth factor (FGF) signaling, and compare and contrast these two different cell migration processes: mesoderm spreading and CVM migration. In both cases, FGF acts as a chemoattractant to guide cells’ directional movement but is likely not the only signal that serves this role. Furthermore, FGF likely modulates cell adhesion properties since FGF mutant phenotypes share similarities with those of cell adhesion molecules. Our working hypothesis is that levels of FGF signaling differentially influence cells’ response to result in either directional movement or changes in adhesive properties.     

Polo-like kinase 1 (Plk1) is expressed by cutaneous T-cell lymphomas (CTCLs), and its downregulation promotes cell cycle arrest and apoptosis

Polo-like kinases are serine/threonine kinases crucial for mitosis and DNA integrity. Plk1, the most well studied member of this family, is upregulated in several cancers, as well as in dividing cells with peak expression during G2/M phase. Recently, employing lesional skin from patients with cutaneous T-cell lymphoma (CTCL), we showed that Plk1 was increased mainly in advanced lesions. In this study, employing western blot and quantitative RT-PCR analyses, we demonstrated that Plk1 was overexpressed in multiple CTCL cell lines (HH, Hut78, MyLa, SeAx and SZ4). Further, a genetic knockdown (by short hairpin RNA) or enzyme activity inhibition (via a small molecule inhibitor, GW843682X) was found to result in a decrease in cell growth, viability and proliferation. Plk1 inhibition in CTCL cells also resulted in: (1) increased G2/M phase cell cycle arrest, (2) alteration in key mitotic proteins, (3) apoptosis and (4) multiple mitotic errors. Given our findings, clinical trials of Plk1 inhibitors in CTCL may be a promising area for further translational investigation. We speculate that overexpression of Plk1 may prove to be relevant to the progression and prognosis of CTCL through its direct impact on the regulation of tumor cell proliferation and indirect influence on the acquisition of somatic mutations by proliferating tumor cells.     

α5-nAChR modulates melanoma growth through the Notch1 signaling pathway

The roles of α5-nicotinic acetylcholine receptors (α5-nAChRs) in various types of solid cancer have been reported; however, its role in melanoma remains unknown. We knocked down α5-nAChR expression in melanoma cells to investigate the role of α5-nAChR in the proliferation, migration, and invasion of melanoma cells, and its effect on downstream signaling pathways. Using immunohistochemical analysis, we determined that α5-nAChR expression is significantly increased in human melanoma tissues and cell lines compared with normal human skin tissues. Knocking down α5-nAChR expression in melanoma cells in culture significantly inhibited the proliferation, migration, and invasiveness of melanoma cell lines. Specifically, knockdown of α5-nAChR inhibited PI3K-AKT and ERK1/2 signaling activity. Moreover, we confirmed that the Notch1 signaling pathway is the downstream target of α5-nAChR in melanoma. Our findings suggest that α5-nAChR plays a critical role in melanoma development and progression, and that targeting α5-nAChR may be a strategy for melanoma treatment.     

Highlighting Young Investigators: Guest Editor Ramanuj DasGupta Ram DasGupta: Pushing the boundaries of β-catenin signaling and drug development

Abstract

From generating the TOP-GAL mouse to pioneering high-throughput RNAi, and small molecule chemical genetic screens in Drosophila and mammalian cells, Ram DasGupta has consistently developed innovative technological tools of immense value to the fields in which he has chosen to work.