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Lokendra Gupta MDS I.N. Aparna MDS B. Dhanasekar MDS Abhay T. Kamath MDS D. Lingeshwar MDS Priyanka Agarwal BDS 《Journal of prosthodontics》2013,22(3):223-225
Fractures involving pediatric jaws most often require a splint to prevent the fragments from being displaced; however, impression making presents a challenge. This article describes the fabrication of a surgical splint over an ideal cast, which is subsequently refitted with a tissue conditioner onto the patient's jaw. The highlight of this technique is the elimination of an impression procedure, thereby reducing clinical and laboratory time and easing pain in the child. 相似文献
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Yong Zhou Priyanka S. Prakash Hong Liang Alemayehu A. Gorfe John F. Hancock 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(6)
KRAS interacts with the inner leaflet of the plasma membrane (PM) using a hybrid anchor that comprises a lysine-rich polybasic domain (PBD) and a C-terminal farnesyl chain. Electrostatic interactions have been envisaged as the primary determinant of interactions between KRAS and membranes. Here, we integrated molecular dynamics (MD) simulations and superresolution spatial analysis in mammalian cells and systematically compared four equally charged KRAS anchors: the wild-type farnesyl hexa-lysine and engineered mutants comprising farnesyl hexa-arginine, geranylgeranyl hexa-lysine, and geranylgeranyl hexa-arginine. MD simulations show that these equally charged KRAS mutant anchors exhibit distinct interactions and packing patterns with different phosphatidylserine (PtdSer) species, indicating that prenylated PBD–bilayer interactions extend beyond electrostatics. Similar observations were apparent in intact cells, where each anchor exhibited binding specificities for PtdSer species with distinct acyl chain compositions. Acyl chain composition determined responsiveness of the spatial organization of different PtdSer species to diverse PM perturbations, including transmembrane potential, cholesterol depletion, and PM curvature. In consequence, the spatial organization and PM binding of each KRAS anchor precisely reflected the behavior of its preferred PtdSer ligand to these same PM perturbations. Taken together these results show that small GTPase PBD-prenyl anchors, such as that of KRAS, have the capacity to encode binding specificity for specific acyl chains as well as lipid headgroups, which allow differential responses to biophysical perturbations that may have biological and signaling consequences for the anchored GTPase.KRAS4B (hereafter KRAS) is a lipid-anchored small GTPase that regulates multiple signaling pathways to control cell proliferation, survival, and migration (1, 2). KRAS is one of the most frequently mutated proteins in cancer, with mutations found in 98% of pancreatic tumors, 45% of colorectal tumors, and 31% of lung tumors (1, 2). KRAS signaling is mostly compartmentalized to the plasma membrane (PM) (3), where KRAS interacts with a specific set of lipids and undergoes spatial segregation to form nanometer-sized domains, termed nanoclusters (4, 5). Nanoclusters operate as transient platforms for KRAS signal transmission such that the extent of nanoclustering directly correlates with the efficiency of effector recruitment and MAPK signal output (6–8). KRAS effectors require synergistic binding with activated KRAS and specific lipids for efficient PM recruitment and activation (9), therefore concentrating a specific set of lipids within nanoclusters is essential to KRAS function (10, 11). In this context the KRAS C-terminal membrane anchor, which comprises a hexa-lysine polybasic domain (PBD) and a farnesylated, methylesterified cysteine residue (4, 5, 12, 13), selectively sorts the monovalent anionic phospholipid phosphatidylserine (PtdSer) into nanoclusters (7, 11, 14). In consequence, PtdSer levels in the PM modulate the extent of KRAS localization to, and nanoclustering on, the PM and hence regulate KRAS-dependent effector recruitment and signaling (7, 11, 14). Depletion of PtdSer compromises the proliferation of KRAS-driven cancer cell lines and KRAS oncogenicity in mouse xenograft models (15–20). Thus, PtdSer is a key structural component of KRAS signaling nanoclusters on the PM and plays important roles in KRAS function and pathology.Electrostatics have long been considered to be the primary determinant of interactions between anionic lipids and the PBD of KRAS; however, in biological membranes these interactions are more complex. For example, KRAS nanoclusters are enriched with monovalent PtdSer, but not multivalent phosphoinositol 4,5-bisphosphate (PIP2) or phosphoinositol 3,4,5-trisphosphate (PIP3) (7, 11, 14, 21). Moreover, the KRAS anchor selectively binds and sorts mixed-chain PtdSer species comprising one saturated and one unsaturated acyl chain (16:0/18:1 PtdSer and 18:0/18:1 PtdSer), but not symmetric PtdSer species comprising two identical saturated or unsaturated acyl chains (di18:0 PtdSer, di18:1 PtdSer or di18:2 PtdSer) (11, 21). Molecular dynamics (MD) simulations reveal that the KRAS PBD samples diverse conformational states on bilayers (11), including a pseudohelical hairpin with only its center portion inserted into the bilayer core (11, 22). These findings suggest that the KRAS PBD anchor interacts with membranes in complex manners that extend beyond electrostatics. Here, we formally examine this hypothesis by integrating atomistic MD simulations with quantitative electron microscopy (EM)-spatial analysis of intact PM. We show that the KRAS prenyl group and PBD sequence synergistically contribute to the structure and lipid-binding pattern of the anchor on membranes. Different combinations of PBD sequence and prenyl chain can be engineered to preferentially interact with PtdSer species that have different acyl chain structures. When grafted onto KRAS the PtdSer acyl chain binding preferences of these anchors result in fundamentally different responses to multiple biophysical perturbations of PM properties, including transmembrane potential (ΔVm), cholesterol content, and membrane curvature. Together these results show that PBD prenyl anchors by recognizing phospholipid acyl chain structure link PM biophysics to small GTPase spatiotemporal organization and potentially biological function. 相似文献
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Priyanka Vedak B.A. Rosalynn M. Nazarian M.D. Daniela Kroshinsky M.D. M.P.H. 《Pediatric dermatology》2015,32(2):291-292
Eczematid‐like purpura of Doucas and Kapetanakis is a subtype of the pigmented purpuric dermatoses, a group of uncommon dermatoses of unclear etiology characterized by purpura, petechiae, and hyperpigmentation. The Doucas and Kapetanakis subtype is rare in children, and its subtle findings can initially be overlooked and mistaken for other, more common dermatologic disorders in this age group. We present a case eczematid‐like purpura of Doucas and Kapetanakis in an 11‐year‐old boy initially treated as eczema. 相似文献
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The most common type of vascular malformation is the venous malformation and these are occasionally associated with phleboliths. We report a case of a 45 year old woman with intraoral venous malformation with phleboliths. 相似文献
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