Institution
Eli Lilly and Company
Company•Indianapolis, Indiana, United States•
About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.
Topics: Population, Receptor, Placebo, Insulin, Agonist
Papers published on a yearly basis
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TL;DR: Monitoring the dynamic palmitate cycling on synaptic scaffold PSD-95 demonstrated that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals.
Abstract: Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals.
196 citations
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TL;DR: The identification and characterization of a murine gene that encodes an acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1) represents the first identified cardiolipIn-remodeling enzyme from any living organism; its identification implies a novel role for the endoplasmic reticulum in cardiolips metabolism.
196 citations
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TL;DR: There was a significant increase in costs associated with an increase in disease severity as measured by the Kurtzke Expanded Disability Status Scale (EDSS) score and the increase in magnitude was coupled with changes in the distribution of costs.
Abstract: Multiple sclerosis (MS) is a disease of the CNS, typically striking adults during the primary productive time of their life. The symptoms of MS can restrict the individual’s physical activity and income-earning ability, resulting in a major financial burden on the patient, family, health system and society. This systematic literature review was conducted to document the economic burden of MS. Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches were conducted in MEDLINE, EMBASE, PsycINFO, the Health Economic Evaluations Database (HEED), the NHS Economic Evaluation Database (EED) and the UK National Institute for Health and Clinical Excellence (NICE) website as well as conference abstracts. We identified 29 cost-of-illness studies that met the a priori inclusion criteria. The cost categories responsible for the majority of costs associated with MS varied across countries. There was a significant increase in costs associated with an increase in disease severity as measured by the Kurtzke Expanded Disability Status Scale (EDSS) score. The increase in magnitude was coupled with changes in the distribution of costs; although direct medical costs were important contributors in earlier stages of disease, they were outweighed by indirect costs in later stages, mainly due to relapses and productivity losses. Considering the increased costs associated with relapse occurrence and increasing disease severity, pharmaceutical or non-pharmaceutical interventions aimed at delaying the progression of disease may help to reduce the economic burden of MS.
196 citations
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TL;DR: It is demonstrated that transient focal cerebral ischemia results in activation ofNF-kB in neurons and supports previous observations that neuroprotective antioxidants may inhibit neuronal death by preventing the activation of NF-kB.
Abstract: Nuclear factor-kappa B (NF-kappaB) is a multisubunit transcription factor that when activated induces the expression of genes encoding acute-phase proteins, cell adhesion molecules, cell surface receptors, and cytokines. NF-kappaB is composed of a variety of protein subunits of which p50-and p65-kDa (RelA) are the most widely studied. Under resting conditions, these subunits reside in the cytoplasm as an inactive complex bound by inhibitor proteins, IkappaB alpha and IkappaB beta. On activation, IkappaB is phosphorylated by IkappaB kinase and ubiquitinated and degraded by the proteasome; simultaneously, the active heterodimer translocates to the nucleus where it can initiate gene transcription. In the periphery, NF-kappaB is involved in inflammation through stimulation of the production of inflammatory mediators. The role of NF-kappaB in the brain is unclear. In vitro, NF-kappaB activation can be either protective or deleterious. The role of NF-kappaB in ischemic neuronal cell death in vivo was investigated. Adult male rats were subjected to 2 hours of focal ischemia induced by middle cerebral artery occlusion (MCAO). At 2, 6, and 12 hours after reperfusion, the expression and transactivation of NF-kappaB in ischemic versus nonischemic cortex and striatum were determined by immunocytochemistry and by electrophoretic mobility gel-shift analysis. At all time points studied, p50 and p65 immunoreactivity was found exclusively in the nuclei of cortical and striatal neurons in the ischemic hemisphere. The contralateral nonischemic hemisphere showed no evidence of nuclear NF-kappaB immunoreactivity. Double immunofluorescence confirmed expression of p50 in nuclei of neurons. Increased NF-kappaB DNA-binding activity in nuclear extracts prepared from the ischemic hemisphere was further substantiated by electrophoretic mobility gel-shift analysis. Because the activation of NF-kappaB by many stimuli can be blocked by antioxidants in vitro, the effect of the antioxidant, LY341122, previously shown to be neuroprotective, on NF-kappaB activation in the MCAO model was evaluated. No significant activation of NF-kappaB was found by electrophoretic mobility gel-shift analysis in animals treated with LY341122. These results demonstrate that transient focal cerebral ischemia results in activation of NF-kappaB in neurons and supports previous observations that neuroprotective antioxidants may inhibit neuronal death by preventing the activation of NF-kappaB.
196 citations
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TL;DR: Results indicate that this SIS graft was similar to saphenous vein graft in the dog, which had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis.
Abstract: A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog.
196 citations
Authors
Showing all 17866 results
Name | H-index | Papers | Citations |
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Mark J. Daly | 204 | 763 | 304452 |
Irving L. Weissman | 201 | 1141 | 172504 |
Eric J. Topol | 193 | 1373 | 151025 |
Tony Hunter | 175 | 593 | 124726 |
Xiang Zhang | 154 | 1733 | 117576 |
Jerrold M. Olefsky | 143 | 595 | 77356 |
Stephen F. Badylak | 133 | 530 | 57083 |
George A. Bray | 131 | 896 | 100975 |
Lloyd Paul Aiello | 131 | 506 | 85550 |
Levi A. Garraway | 129 | 366 | 99989 |
Mark Sullivan | 126 | 802 | 63916 |
James A. Russell | 124 | 1024 | 87929 |
Tony L. Yaksh | 123 | 806 | 60898 |
Elisabetta Dejana | 122 | 430 | 48254 |
Hagop S. Akiskal | 118 | 565 | 50869 |