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Paul Ahlquist - One of the best experts on this subject based on the ideXlab platform.
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An Amphipathic a-Helix Controls Multiple Roles of Brome Mosaic Virus Protein 1a in RNA Replication Complex Assembly and Function
2016Co-Authors: Ling Liu, Arturo Diaz, Johan Den A Boon, Xiaofeng Wang, William M Westler, Adam H Steinberg, Paul AhlquistAbstract:Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane Invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2aPol) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic a-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane Invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2aPol accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane Invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2aPol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show tha
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an amphipathic α helix controls multiple roles of brome mosaic virus protein 1a in rna replication complex assembly and function
PLOS Pathogens, 2009Co-Authors: Ling Liu, Arturo Diaz, Johan Den A Boon, Paul Ahlquist, Xiaofeng Wang, William M Westler, Adam H SteinbergAbstract:Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane Invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2aPol) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic α-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane Invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2aPol accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane Invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2aPol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.
Jimmy Saunders - One of the best experts on this subject based on the ideXlab platform.
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differences in the morphology of distal border synovial Invaginations of the distal sesamoid bone in the horse as evaluated by computed tomography compared with radiography
Equine Veterinary Journal, 2012Co-Authors: Sarah Claerhoudt, Hendrikjan Bergman, H Van Der Veen, Luc Duchateau, Els Raes, Jimmy SaundersAbstract:Reasons for performing study: Distal border synovial Invaginations of the distal sesamoid bone are radiographically assessed during the selection process of horses admitted as breeding stallions or in purchase examinations. Nowadays, many moderately or some deeply penetrating proximally enlarged synovial Invaginations are considered as moderate or severe radiographic findings. Objective: To measure the difference between and agreement of the morphology of distal border synovial Invaginations on radiography vs. computed tomography (CT). It was hypothesised that the morphology of distal border synovial Invaginations would be better evaluable on CT compared with radiography. Methods: Computed tomography scans and 3 dorsoproximal-palmarodistal oblique (DPr-PaDiO) radiographs were obtained on 50 cadaver forefeet from 25 Warmblood horses. Computed tomography was assumed to be the gold standard. The number, shape and depth of penetration of distal border synovial Invaginations into the distal sesamoid bone were evaluated with both methods, and the comparison of their measurements was statistically described. Results: A statistically significant mean difference for number of distal synovial Invaginations between CT and all 3 DPr-PaDiO projections was found and was approximately equal to 2, meaning that CT permits visualisation of an average of 2 more Invaginations than radiography. In none of the cases did radiography have a higher number observed than CT. A large variation in the difference of measurements for depth of penetration against their mean difference between CT and the 3 radiographic projections was seen. Radiography underestimated the depth of Invaginations, and more so when these were deeper. There was no statistically significant mean difference found between the techniques for depth. A moderate to good agreement between measurements on CT and the three DPr-PaDiO projections for shape was seen, in which the D55°Pr-PaDiO projection showed the best agreement. A high specificity (90-99%) and low sensitivity (65%) for all projections for shape were found. Conclusions and potential relevance: Radiography differs considerably from CT concerning the morphology of distal navicular border synovial Invaginations. For the evaluation of the number, depth and shape of distal synovial Invaginations in the distal sesamoid bone, radiography shows only partially the morphology seen on CT.
Winfried Romer - One of the best experts on this subject based on the ideXlab platform.
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gm1 structure determines sv40 induced membrane Invagination and infection
Nature Cell Biology, 2010Co-Authors: Helge Ewers, Winfried Romer, Alicia E Smith, Kirsten Bacia, Serge Dmitrieff, Wengang Chai, Roberta Mancini, Jurgen KartenbeckAbstract:It is unclear whether viral particles can induce membrane curvature. Binding of Simian virus 40 (SV40) to the GM1 ganglioside on host plasma membranes leads to membrane curvature and the formation of Invaginations in cells and in giant unilamellar vesicles, an effect required for viral infection. Incoming simian virus 40 (SV40) particles enter tight-fitting plasma membrane Invaginations after binding to the carbohydrate moiety of GM1 gangliosides in the host cell plasma membrane through pentameric VP1 capsid proteins. This is followed by activation of cellular signalling pathways, endocytic internalization and transport of the virus via the endoplasmic reticulum to the nucleus. Here we show that the association of SV40 (as well as isolated pentameric VP1) with GM1 is itself sufficient to induce dramatic membrane curvature that leads to the formation of deep Invaginations and tubules not only in the plasma membrane of cells, but also in giant unilamellar vesicles (GUVs). Unlike native GM1 molecules with long acyl chains, GM1 molecular species with short hydrocarbon chains failed to support such Invagination, and endocytosis and infection did not occur. To conceptualize the experimental data, a physical model was derived based on energetic considerations. Taken together, our analysis indicates that SV40, other polyoma viruses and some bacterial toxins (Shiga and cholera) use glycosphingolipids and a common pentameric protein scaffold to induce plasma membrane curvature, thus directly promoting their endocytic uptake into cells.
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shiga toxin induces tubular membrane Invaginations for its uptake into cells
Nature, 2007Co-Authors: Winfried Romer, Ludwig Berland, Valerie Chambon, Katharina Gaus, Barbara Windschiegl, Daniele Tenza, Mohamed R E Aly, Vincent FraisierAbstract:Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane Invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane Invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the Invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.
Atul Goel - One of the best experts on this subject based on the ideXlab platform.
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basilar Invagination chiari malformation syringomyelia a review
Neurology India, 2009Co-Authors: Atul GoelAbstract:Institute and personal experience (over 25 years) of basilar Invagination was reviewed. The database of the department included 3300 patients with craniovertebral junction pathology from the year 1951 till date. Patients with basilar Invagination were categorized into two groups based on the presence (Group A) or absence (Group B) of clinical and radiological evidence of instability of the craniovertebral junction. Standard radiological parameters described by Chamberlain were used to assess the instability of the craniovertebral junction. The pathogenesis and clinical features in patients with Group A basilar Invagination appeared to be related to mechanical instability, whereas it appeared to be secondary to embryonic dysgenesis in patients with Group B basilar Invagination. Treatment by facetal distraction and direct lateral mass fixation can result in restoration of craniovertebral and cervical alignment in patients with Group A basilar Invagination. Such a treatment can circumvent the need for transoral or posterior fossa decompression surgery. Foramen magnum bone decompression appears to be a rational surgical treatment for patients having Group B basilar Invagination. The division of patients with basilar Invagination on the basis of presence or absence of instability provides insight into the pathogenesis of the anomaly and a basis for rational surgical treatment.
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Progressive basilar Invagination after transoral odontoidectomy: treatment by atlantoaxial facet distraction and craniovertebral realignment.
Spine, 2005Co-Authors: Atul GoelAbstract:STUDY DESIGN The issue of progression of congenital basilar Invagination is evaluated on the basis of 3 clinical cases. The rationale of treatment of basilar Invagination in general and, particularly, in the complex clinical situation encountered in the presented cases, by the authors' technique of atlantoaxial joint distraction, reduction of basilar Invagination, and direct lateral mass plate and screw fixation is discussed. OBJECTIVE The subject of progression of congenital basilar Invagination and recurrent craniocervical cord compression after an initial transoral decompression is analyzed, and an alternative surgical treatment involving craniovertebral bone realignment is suggested. SUMMARY OF BACKGROUND DATA This is a review of 3 cases of basilar Invagination treated earlier by transoral decompression. No fixation procedure was performed. The patients presented with recurrent symptoms of high cervical cord compression. Investigations revealed a progression of basilar Invagination and cord compression. The treatment of such a complex clinical situation by atlantoaxial joint distraction is discussed. METHODS Between September 2001 and January 2004, we treated 3 patients with congenital basilar Invagination who underwent transoral odontoidectomy but did not undergo any posterior atlantoaxial or occipitoaxial fixation. The patients had postoperative improvement but worsening of their neurologic condition after an average duration of 26 months after transoral surgery. Repeat investigations revealed that basilar Invagination and the craniovertebral alignments worsened during the period, and there was recurrent cervicomedullary cord compression. These patients were treated by atlantoaxial facet distraction, and attempts were made toward reduction of the basilar Invagination and craniovertebral junction bony realignment, and atlantoaxial fixation by the technique recently described by us. RESULTS During the average follow-up of 25 months, all 3 patients have had a neurologic recovery. CONCLUSIONS The probable cause of basilar Invagination and its progression is a congenital malformation ofalignment of the facets of the atlantoaxial joint. Distraction of the facets and direct interarticular atlantoaxial fixation presents a unique opportunity of reduction of the basilar Invagination and fixation of the region.
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Treatment of basilar Invagination by atlantoaxial joint distraction and direct lateral mass fixation
Journal of neurosurgery. Spine, 2004Co-Authors: Atul GoelAbstract:Object. The author discusses the successful preliminary experience of treating selected cases of basilar Invagination by performing atlantoaxial joint distraction, reduction of the basilar Invagination, and direct lateral mass atlantoaxial plate/screw fixation. Methods. Twenty-two patients with basilar Invagination—in which the odontoid process invaginated into the foramen magnum and the tip of the odontoid process was above the Chamberlain, McRae foramen magnum, and Wackenheim clival lines—were selected to undergo surgery. In all patients fixed atlantoaxial dislocations were documented. The 16 male and six female patients ranged in age from 8 to 50 years. A history of trauma prior to the onset of symptoms was documented in 17 patients. Following surgery, the author observed minimal-to-significant reduction of basilar Invagination and alteration in other craniospinal parameters resulting in restoration of alignment of the tip of the odontoid process and the clivus and the entire craniovertebral junction i...
Ling Liu - One of the best experts on this subject based on the ideXlab platform.
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An Amphipathic a-Helix Controls Multiple Roles of Brome Mosaic Virus Protein 1a in RNA Replication Complex Assembly and Function
2016Co-Authors: Ling Liu, Arturo Diaz, Johan Den A Boon, Xiaofeng Wang, William M Westler, Adam H Steinberg, Paul AhlquistAbstract:Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane Invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2aPol) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic a-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane Invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2aPol accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane Invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2aPol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show tha
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an amphipathic α helix controls multiple roles of brome mosaic virus protein 1a in rna replication complex assembly and function
PLOS Pathogens, 2009Co-Authors: Ling Liu, Arturo Diaz, Johan Den A Boon, Paul Ahlquist, Xiaofeng Wang, William M Westler, Adam H SteinbergAbstract:Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane Invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2aPol) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic α-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane Invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2aPol accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane Invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2aPol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.
