Altered GABAergic inhibitory tone has been observed in association with a number of both acute and chronic models of epilepsy and is believed to be the result, in part, of a decrease in function of the postsynaptic GABA A receptor (GABA A R). This study was carried out to investigate if alterations in receptor internalization contribute to the decrease in GABA A R function observed with epilepsy, utilizing the hippocampal neuronal culture model of low-Mg 2ϩ -induced spontaneous recurrent epileptiform discharges (SREDs). Analysis of GABA A R function in "epileptic" cultures showed a 62% reduction in [ 3 H]flunitrazepam binding to the GABA A ␣ receptor subunit and a 50% decrease in GABA currents when compared with controls. Confocal microscopy analysis of immunohistochemical staining of GABA A R 2/3 subunit expression revealed approximately a 30% decrease of membrane staining in hippocampal cultures displaying SREDs immediately after low-Mg 2ϩ treatment and in the chronic epileptic state. Low-Mg 2ϩ -treated cultures internalized antibody labeled GABA A receptor with an increase in rate of 68% from control. Inhibition of GABA A R endocytosis in epileptic cultures resulted in both a recovery to control levels of membrane GABA A 2/3 immunostaining and a total blockade of SREDs. These results indicate that altered GABA A R endocytosis contributes to the decrease in GABA A R expression and function observed in this in vitro model of epilepsy and plays a role in causing and maintaining SREDs. Understanding the mechanisms underlying altered GABA A R recycling may offer new insights into the pathophysiology of epilepsy and provide novel therapeutic strategies to treat this major neurological condition.
In March 2005, U.S. authorities informed the European Commission of the inadvertent release of unauthorized maize GM event Bt10 in their market and subsequently the grain channel. In the United States measures were taken to eliminate Bt10 from seed and grain supplies; in the European Union an embargo for maize gluten and brewer's grain import was implemented unless certified of Bt10 absence with a Bt10-specific PCR detection method. With the aim of assessing the validity of the Bt10 detection method, an in-depth analysis of the molecular organization of the genetic modification of this event was carried out by both the company Syngenta, who produced the event, and the European Commission Joint Research Centre, who validated the detection method. Using a variety of molecular analytical tools, both organizations found the genetic modification of event Bt10 to be very complex in structure, with rearrangements, inversions, and multiple copies of the structural elements (cry1Ab, pat, and the amp gene), interspersed with small genomic maize fragments. Southern blot analyses demonstrated that all Bt10 elements were found tightly linked on one large fragment, including the region that would generate the event-specific PCR amplicon of the Bt10 detection method. This study proposes a hypothetical map of the insert of event Bt10 and concludes that the validated detection method for event Bt10 is fit for its purpose.
This section describes several of the sensor input sources of information that may be required. However, the system is highly configurable, so these sources and policies can change at each installation site. 2.2.1 Cyber Security Event Information Event information typically available within the cybersecurity system continues to play a key role in detecting anomalous system activities. Monitoring The cybersecurity system monitors devices using an agent installed on those it is protecting. It can monitor files, running processes, events, and network communications. It can take action locally, such as restarting a stopped process, or preventing unknown processes from starting. Bill of Health The system can centrally store a fingerprint (cryptographic signature) of monitored items to identify unauthorized changes. This is included in an overall "Bill of Health" measure of the expected configuration of each device. This adds some overhead in making approved changes, since the operator must compute and store the new approved signature. However, correlation of changed configuration without approval is a reasonable trigger to take action. Network Alarms The central security services can receive network alarms through SNMP or other means. The auto-response policies can use this information to correlate events and determine likelihood of attacks or suspicious activity.
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