Abstract-The carboxyl-terminal domain of connexin43 (Cx43CT) is involved in various intra-and intermolecular interactions that regulate gap junctions. Here, we used phage display to identify novel peptidic sequences that bind Cx43CT and modify Cx43 regulation. We found that Cx43CT binds preferentially to peptides containing a sequence RXP, where X represents any amino acid and R and P correspond to the amino acids arginine and proline, respectively.A biased "RXP library" led to the identification of a peptide (dubbed "RXP-E") that bound Cx43CT with high affinity. Nuclear magnetic resonance data showed RXP-E-induced shifts in the resonance peaks of residues 343 to 346 and 376 to 379 of Cx43CT. Patch-clamp studies revealed that RXP-E partially prevented octanol-induced and acidificationinduced uncoupling in Cx43-expressing cells. Moreover, RXP-E increased mean open time of Cx43 channels. The full effect of RXP-E was dependent on the integrity of the CT domain. These data suggest that RXP-based peptides could serve as tools to help determine the role of Cx43 as a regulator of function in conditions such as ischemia-induced arrhythmias. (Circ Res. 2006;98:1365-1372.)Key Words: Cx43CT Ⅲ connexin Ⅲ particle-receptor interaction Ⅲ gap junctions C onnexins are integral membrane proteins that oligomerize to form intercellular channels called gap junctions. The most abundant gap junction protein in a number of mammalian systems is connexin43 (Cx43). Our previous work has suggested that regulation of Cx43 channels results from the association of the carboxyl-terminal (CT) domain, acting as a gating particle, and a separate region of the connexin molecule, acting as a receptor for the gating particle. 1,2 Additional studies have shown that this intramolecular interaction can be modulated by other intermolecular interactions in the microenvironment of the gap junction plaque. 3 Thus, the emerging picture of a gap junction plaque is that of a macromolecular complex in which proteins act in concert to modulate intercellular communication. At the center of these interactions is the CT domain, which acts as a substrate for a number of kinases, 4 a ligand for noncatalytic proteins, and a gating particle to modify coupling between cells. 5 As a key player in the regulation of gap junctions, CT presents itself as a target of chemical 6,7 or genetic manipulation intended to modify function. 8 Here, we sought to disrupt the regulation of Cx43 by chemical means. Our rationale was based on the knowledge that Cx43CT is capable of interacting with other proteins. We reasoned that this "stickiness" of Cx43CT can be used to "adhere" peptidic sequences to it. We further speculated that the interaction of Cx43CT with small peptides can modify the behavior of the gap junction channel. This rationale was supported by previous work showing that peptides can modify both the chemical and voltage-gating behavior of Cx43. 6,7 In the present study, we used a highthroughput phage display screening to find peptidic sequences that bind Cx43CT. Furth...

Following the allocation of the procurement of the diagnostic neutral beam (DNB) to the Indian DA, a series of tasks have been undertaken to first assess the DNB configuration and arrive at an optimal beam-line configuration folding in the gas-feed and vacuum-pumping requirements. Specific emphasis is placed on the thermal, structural, and electrical designs of beam-line components, in order to ensure their compatibility with the criteria specified for ITER in vessel components, i.e., Structural Design Criteria for In-Vessel Components. The detailed assessment of manufacturing technologies and their compatibility with the ITER standards forms an integral part of the design. A common approach to manufacturing for DNB and heating-and-current-drive NB components shall be undertaken through a comprehensive prototyping phase which shall lead to built-to-print specifications. In addition to safety and remote-handling issues, the design also addresses the requirements of interfaces related to other systems such as cryo, hydraulic, pneumatic, vacuum pumping, gas feed, civil, power supplies and transmission, CODAC, etc. The successful delivery of DNB is dependent on two critical R&D aspects: 1) the production of a uniform low-divergence beam from the beam source and 2) a well-controlled transmission through lengths of ∼22 m. The first shall primarily be a subject of the Ion Source Test Facility-SPIDER [part of NB test facility (MITICA in Padova)]-where India is involved as a collaborator and the Indian test bed, where issues for DNB beam source which were not resolved in the SPIDER would be taken up. The second shall form one of the primary objectives of the Indian test bed to characterize the DNB. This paper presents the progress in DNB from the concept level to an engineered system along with the plans for system integration and an R&D intensive implementation.Index Terms-Beam transmission, beam-line components (BLCs), concept, diagnostic neutral beam (NB) (DNB), ITER.

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Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.