Paley E.L.,Nova Southeastern University |
Paley E.L.,Expert Inc.
Translational Oncology | Year: 2011
Tryptophanyl-tRNA synthetase (TrpRS) expression alters in colorectal (CRC), pancreatic (PC), and cervical (CC) cancers. Here, phosphorylation of unfolded TrpRS and its fragments is stimulated by human cancer sera (CS; n = 13) and serum of rabbit tumor induced by Rous sarcoma virus, unaffected by donor sera (NS; 11/15) and abolished by alkaline phosphatase. At 20 years of follow-up, serum-inducible TrpRS phosphorylation found years before healthy donors (3/15) diagnosed with PC, CRC, or leukemia. I have examined a specificity of serum-inducible TrpRS phosphorylation and found, surprisingly, that serine phosphorylation of unfolded TrpRS is stimulated by anti-TrpRS rabbit antisera but is unaffected by rabbit nonimmune sera and antisera to other antigens. Anti-TrpRS immunoglobulin G (IgG) inhibits phosphorylation of full-length TrpRS and stimulates phosphorylation of its 20-kDa fragment. Phosphorylation of this fragment is stimulated also by CS but not NS. 2-Mercaptoethanol and cyclic AMP exerted synergistic inhibitory effect on TrpRS phosphorylation. Anti-TrpRS sera and casein act as chaperones increasing TrpRS phosphorylation through refolding. Histone-specific protein kinase activity in CS (n = 44) and anti-TrpRS sera was lower than that in NS (n=11), rabbit nonimmune sera and antisera to other antigens. TrpRS inhibitors, tryptamine, and tryptophanol stimulate in vivo accumulation of enzymatically inactive, nonphosphorylated, aggregated and anti-TrpRS IgG refoldable TrpRS. Phosphorylation of postsurgical tissues (n = 18) reveals TrpRS in ovarian cancer (OVC) and CC but not in normal placenta and liver. In OVC, TrpRS phosphorylation increase correlates with elevated tryptophan-dependent ATP-inorganic pyrophosphate exchange. Although not inducing cancer, TrpRS triggers signaling concomitant with cancer. © 2011 Neoplasia Press, Inc. Source
Paley E.L.,Nova Southeastern University |
Paley E.L.,Expert Inc. |
Perry G.,University of Texas at San Antonio |
Sokolova O.,Brandeis University
Current Alzheimer Research | Year: 2013
Neurodegeneration is induced by tryptamine, a human diet constituent, which easily crosses the blood/brain barrier. Tryptamine neurotoxicity, caused by tryptophanyl-tRNA synthetase (TrpRS) inhibition and downregulation leads to tryptophanyl-tRNA deficiency and synthesis of aberrant proteins. We identified axonal defects in hippocampus of tryp-tamine-treated mice similar to those observed in human brain of patients with Alzheimer's disease, multiple sclerosis and epilepsy using anti-TrpRS site-directed antibodies. The axonal defects are characterized by swellings that accumulate abnormal amounts of helical filaments and amyloid. Tryptamine produced a decreased density of somatic mitochondria concomitant with neuronal loss in mouse hippocampus. In addition, tryptamine evoked accumulation and clustering of small mitochondria in mouse hippocampus causing axonal swellings. Similarly, mitochondrial fission, fusion and clustering were revealed in human neuronal cells after tryptamine administration. Moreover the tryptamine-induced mitochondrial neuropathology includes electron-dense deposits comprising helical fibrils, cristae disruption, cristolysis, mitochondrial swelling and mitochondria-derived vesicles. TrpRS+ helical filamentous tangles formed in both neuronal and kidney cells following tryptamine treatment suggest a tryptamine broad cytotoxic repertoire in damaging vital organs. Tryptamine elicited vesicularization of inner and outer mitochondrial membranes, axonal and cell membranes. Ultrastructurally, fragmentation of swollen degenerated mitochondria, small mitochondria clustering and neurofibrillary tangles are associated with axonal membrane protrusions attributed as neuritic swellings at a lower magnification. TrpRS+ axonal swellings associated with neuropathology of patients and tryptamine-treated human cells suggest that under toxic concentrations, tryp-tamine is implicated as a causative agent in neurodegeneration resembling that defining a number of human diseases. © 2013 Bentham Science Publishers. Source
Abdo J.,University Paris Diderot |
Serfass J.-P.,Expert Inc. |
Pellevoisin P.,SCREG Ile de France Normand
Road Materials and Pavement Design | Year: 2013
The French road network, 95% of which consists of flexible and semi-rigid pavements, lends itself a priori well to in-place recycling. This article provides a summary of existing knowledge and rules of best practice with respect to the technique of cold in situ pavement reclaiming using hydraulic binders. The various aspects of this process are described in detail. The first approach is structural, it includes pavement mechanics and protection against frost/thaw. The second approach relates to the geometric rehabilitation of the facility. Lastly, the very significant sustainable development aspects are developed. For each of the aspects mentioned above, the general principles, the selection criteria for recycling equipment and binder, the assessment and control methodology are presented. The know-how specific to the various fields of applications is detailed. Typical examples are given. © 2013 © 2013 Taylor & Francis. Source
Agency: Department of Defense | Branch: Special Operations Command | Program: SBIR | Phase: Phase I | Award Amount: 99.73K | Year: 2006
US Special Operations Command has a requirement for effective language training to equip SOF soldiers, sailors and airmen when they are deployed to foreign countries. We propose to create a system which would combine a user-friendly game and real-time interaction with subject matter experts. End users will have a fun, engaging application and also have the chance to engage live langauge experts. This maximizes learning effectiveness with both static and dynamic content.
Agency: Department of Defense | Branch: Special Operations Command | Program: SBIR | Phase: Phase II | Award Amount: 1.46M | Year: 2008
PEC proposes to work on advanced curriculum development in order to integrate into an advanced gaming environment. To this end, PEC will adapt existing USSOCOM curriculum and provide guidance to developers in order to implement the curriculum. In addition, PEC will create avatars which can teach and demonstrate cultural gestures. These avatars will be advanced such that a user can take control of the avatar to interact with other characters.