No abstract

The voltage-dependent conductances of Litnulus ventral photoreceptors have been investigated using a voltage-clamp technique . Depolarization in the dark induces inward and outward currents . The inward current is reduced by removing Na' or Ca2+ and is abolished by removing both ions. These results suggest that both Na' and Ca

The influence of voltage-dependent conductances on the receptor potential of Limulus ventral photoreceptors was investigated . During prolonged, bright illumination, the receptor potential consists of an initial transient phase followed by a smaller plateau phase. Generally, a spike appears on the rising edge of the transient phase, and often a dip occurs between the transient and plateau . Block of the rapidly inactivating outward current, iA, by 4-aminopyridine eliminates the dip under some conditions . Block of maintained outward current by internal tetraethylammonium increases the height of the plateau phase, but does not eliminate the dip. Block of the voltage-dependent Na' and Ca

The Ca ~+ indicator photoprotein, aequorin, was used to estimate and monitor intracellular Ca 2+ levels in Liraulua ventral photoreceptors during procedures designed to affect Na+/Ca ~+ exchange. Dark levels of [Ca~+] Under constant voltage clamp (-80 mV) inward currents were measured after the addition of Na 2 to 0-Na + 0-Ca 2+ saline and outward currents were measured after the addition of Ca2o + to 0-Na + 0-Ca 2+ saline. The results suggest the presence of an electrogenic Na+/Ca ~+ exchange process in the plasma membrane of Limulua ventral photoreceptors that can operate in forward (Na~-dependent Ca 2+ extrusion) or reverse (Nai+-dependent Ca ~+ influx) directions.

Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice.