The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Shyam S. Krishnakumar - One of the best experts on this subject based on the ideXlab platform.
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Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
eLife, 2020Co-Authors: Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, James E. Rothman, Shyam S. KrishnakumarAbstract:Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of 'central' SNARE complexes via the Primary Interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free 'peripheral' SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (
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synergistic roles of synaptotagmin 1 and complexin in calcium regulated neuronal exocytosis
eLife, 2020Co-Authors: Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, James E. Rothman, Shyam S. KrishnakumarAbstract:Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of 'central' SNARE complexes via the Primary Interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free 'peripheral' SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (<100 msec) and synchronous fusion of the docked vesicles.
Sathish Ramakrishnan - One of the best experts on this subject based on the ideXlab platform.
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Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis
eLife, 2020Co-Authors: Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, James E. Rothman, Shyam S. KrishnakumarAbstract:Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of 'central' SNARE complexes via the Primary Interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free 'peripheral' SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (
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synergistic roles of synaptotagmin 1 and complexin in calcium regulated neuronal exocytosis
eLife, 2020Co-Authors: Sathish Ramakrishnan, Manindra Bera, Jeff Coleman, James E. Rothman, Shyam S. KrishnakumarAbstract:Calcium (Ca2+)-evoked release of neurotransmitters from synaptic vesicles requires mechanisms both to prevent un-initiated fusion of vesicles (clamping) and to trigger fusion following Ca2+-influx. The principal components involved in these processes are the vesicular fusion machinery (SNARE proteins) and the regulatory proteins, Synaptotagmin-1 and Complexin. Here, we use a reconstituted single-vesicle fusion assay under physiologically-relevant conditions to delineate a novel mechanism by which Synaptotagmin-1 and Complexin act synergistically to establish Ca2+-regulated fusion. We find that under each vesicle, Synaptotagmin-1 oligomers bind and clamp a limited number of 'central' SNARE complexes via the Primary Interface and introduce a kinetic delay in vesicle fusion mediated by the excess of free SNAREpins. This in turn enables Complexin to arrest the remaining free 'peripheral' SNAREpins to produce a stably clamped vesicle. Activation of the central SNAREpins associated with Synaptotagmin-1 by Ca2+ is sufficient to trigger rapid (<100 msec) and synchronous fusion of the docked vesicles.
Michael Hobbs - One of the best experts on this subject based on the ideXlab platform.
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Virtual World Security Inspection
Journal of Networks, 2012Co-Authors: Nicholas Patterson, Michael HobbsAbstract:Virtual property theft is a serious problem that exists in virtual worlds. Legitimate users of these worlds invest considerable amounts of time, effort and real-world money into obtaining virtual property, but unfortunately, are becoming victims of theft in high numbers. It is reported that there are over 1 billion registered users of virtual worlds containing virtual property items worth an estimated US$50 billion dollars. The problem of virtual property theft is complex, involving many legal, social and technological issues. The software used to access virtual worlds is of great importance as they form the Primary Interface to these worlds and as such the Primary Interface to conduct virtual property theft. The security vulnerabilities of virtual world applications have not, to date, been examined. This study aims to use the process of software inspection to discover security vulnerabilities that may exist within virtual world software – vulnerabilities that enable virtual property theft to occur. Analyzing three well know virtual world applications World of Warcraft, Guild Wars and Entropia Universe, this research utilized security analysis tools and scenario testing with focus on authentication, trading, intruder detection and virtual property recovery. It was discovered that all three examples were susceptible to keylogging, mail and direct trade methods were the most likely method for transferring stolen items, intrusion detection is of critical concern to all VWEs tested, stolen items were unable to be recovered in all cases and lastly occurrences of theft were undetectable in all cases. The results gained in this study present the key problem areas which need to be addressed to improve security and reduce the occurrence of virtual property theft.
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Virtual world security inspection : a software inspection process carried out on popular virtual world environments
2011Co-Authors: Nicholas Patterson, Michael HobbsAbstract:Virtual property theft is a serious problem that exists in virtual worlds. Legitimate users of these worlds invest considerable amounts of time, effort and real-world money into obtaining virtual property, but unfortunately, are becoming victims of theft in high numbers. It is reported that there are over 1 billion registered users of virtual worlds containing virtual property items worth an estimated US$50 billion dollars. The problem of virtual property theft is complex, involving many legal, social and technological issues. The software used to access virtual worlds is of great importance as they form the Primary Interface to these worlds and as such the Primary Interface to conduct virtual property theft. The security vulnerabilities of virtual world applications have not, to date, been examined. This study aims to use the process of software inspection to discover security vulnerabilities that may exist within virtual world software – vulnerabilities that enable virtual property theft to occur. Analyzing three well know virtual world applications World of Warcraft, Guild Wars and Entropia Universe, this research utilized security analysis tools and scenario testing with focus on authentication, trading, intruder detection and virtual property recovery. It was discovered that all three examples were susceptible to keylogging, mail and direct trade methods were the most likely method for transferring stolen items, intrusion detection is of critical concern to all VWEs tested, stolen items were unable to be recovered in all cases and lastly occurrences of theft were undetectable in all cases. The results gained in this study present the key problem areas which need to be addressed to improve security and reduce the occurrence of virtual property theft.
Thomas S. Kupper - One of the best experts on this subject based on the ideXlab platform.
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Immune surveillance in the skin: mechanisms and clinical consequences
Nature reviews. Immunology, 2004Co-Authors: Thomas S. Kupper, Robert C. FuhlbriggeAbstract:The skin, as the Primary Interface between the body and the environment, provides the first line of defence against a broad array of microbial pathogens and trauma. In addition to its properties as a physical barrier, the skin has many active defence mechanisms. In this review, we discuss the interaction between the innate and adaptive immune systems in the skin as a model for immune function at epithelial-cell Interfaces with the environment. How these mechanisms account for the robust nature of cutaneous immune surveillance and how their dysregulation drives the pathogenesis of inflammatory skin disorders and skin-based tumours are the subjects of this review.
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Inflammatory Skin Diseases, T Cells, and Immune Surveillance
The New England journal of medicine, 1999Co-Authors: Caroline Robert, Thomas S. KupperAbstract:Skin is the Primary Interface between the body and the environment. The spectrum of insults to which skin is susceptible includes disorders caused by chemical and microbial agents, thermal and elec...
Amanda S Macleod - One of the best experts on this subject based on the ideXlab platform.
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skin viral infections host antiviral innate immunity and viral immune evasion
Frontiers in Immunology, 2020Co-Authors: Vivian Lei, Amy J Petty, Amber Reck Atwater, Sarah A Wolfe, Amanda S MacleodAbstract:The skin is an active immune organ that functions as the first and largest site of defense to the outside environment. Serving as the Primary Interface between host and pathogen, the skin's early immune responses to viral invaders often determine the course and severity of infection. We review the current literature pertaining to the mechanisms of cutaneous viral invasion for classical skin-tropic, oncogenic, and vector-borne skin viruses. We discuss the skin's evolved mechanisms for innate immune viral defense against these invading pathogens, as well as unique strategies utilized by the viruses to escape immune detection. We additionally explore the roles that demographic and environmental factors, such as age, biological sex, and the cutaneous microbiome, play in altering the host immune response to viral threats.