Institution
Icahn School of Medicine at Mount Sinai
Education•New York, New York, United States•
About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.
Topics: Population, Cancer, Transplantation, Virus, Health care
Papers published on a yearly basis
Papers
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TL;DR: It is found that the growth factor–stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states, and MAPK phosphatase may be critical for this flexible response.
Abstract: Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.
624 citations
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TL;DR: The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.
624 citations
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623 citations
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TL;DR: It is determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo.
Abstract: Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.
623 citations
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TL;DR: Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non–HCM-associated mutants were kinase impaired, which implicate increased RAS signaling in pathological cardiomyocyte hypertrophy.
Abstract: Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy.
623 citations
Authors
Showing all 37948 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert Langer | 281 | 2324 | 326306 |
Shizuo Akira | 261 | 1308 | 320561 |
Gordon H. Guyatt | 231 | 1620 | 228631 |
Eugene Braunwald | 230 | 1711 | 264576 |
Bruce S. McEwen | 215 | 1163 | 200638 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Peter Libby | 211 | 932 | 182724 |
Mark J. Daly | 204 | 763 | 304452 |
Stuart H. Orkin | 186 | 715 | 112182 |
Paul G. Richardson | 183 | 1533 | 155912 |
Alan C. Evans | 183 | 866 | 134642 |
John C. Morris | 183 | 1441 | 168413 |
Paul M. Thompson | 183 | 2271 | 146736 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Bruce M. Psaty | 181 | 1205 | 138244 |