Engineered underdominance as a method of insect population replacement and reproductive isolation

Insect vector-borne diseases, such as malaria and dengue fever (both spread by mosquito vectors), continue to significantly impact health worldwide, despite the efforts put forth to eradicate them. Suppression strategies utilizing genetically modified disease-refractory insects have surfaced as an attractive means of disease control, and progress has been made on engineering disease-resistant insect vectors. However, laboratory-engineered disease refractory genes would probably not spread in the wild, and would most likely need to be linked to a gene drive system in order to proliferate in native insect populations. Underdominant systems like translocations and engineered underdominance have been proposed as potential mechanisms for spreading disease refractory genes. Not only do these threshold-dependent systems have certain advantages over other potential gene drive mechanisms, such as localization of gene drive and removability, extreme engineered underdominance can also be used to bring about reproductive isolation, which may be of interest in controlling the spread of GMO crops. Proof-of-principle establishment of such drive mechanisms in a well-understood and studied insect, such as Drosophila melanogaster, is essential before more applied systems can be developed for the less characterized vector species of interest, such as mosquitoes. This work details the development of several distinct types of engineered underdominance and of translocations in Drosophila, including ones capable of bringing about reproductive isolation and population replacement, as a proof of concept study that can inform efforts to construct such systems in insect disease vectors.

Primary cosmic-ray positrons and negatrons in 1968 at energies between 11 and 204 MeV

The cosmic-ray positron and negatron spectra between 11 and 204 MeV have been measured in a series of 3 high-altitude balloon flights launched from Fort Churchill, Manitoba, on July 16, July 21, and July 29, 1968. The detector system consisted of a magnetic spectrometer utilizing a 1000-gauss permanent magnet, scintillation counters, and a lucite Čerenkov counter.

Launches were timed so that the ascent through the 100 g/cm² level of residual atmosphere occurred after the evening geomagnetic cutoff transition. Data gathered during ascent are used to correct for the contribution of atmospheric secondary electrons to the flux measured at float altitude. All flights floated near 2.4 g/cm².

A pronounced morning intensity increase was observed in each flight. We present daytime positron and negatron data which support the interpretation of the diurnal flux variation as a change in the local geomagnetic cutoff. A large diurnal variation was observed in the count rate of positrons and negatrons with magnetic rigidities less than 11 MV and is evidence that the nighttime cutoff was well below this value.

Using nighttime data we derive extraterrestrial positron and negatron spectra. The positron-to-total-electron ratio which we measure indicates that the interstellar secondary, or collision, source contributes ≾50 percent of the electron flux within this energy interval. By comparing our measured positron spectrum with the positron spectrum calculated for the collision source we derive the absolute solar modulation for positrons in 1968. Assuming negligible energy loss during modulation, we derive the total interstellar electron spectrum as well as the spectrum of directly accelerated, or primary, electrons. We examine the effect of adiabatic deceleration and find that many of the conclusions regarding the interstellar electron spectrum are not significantly altered for an assumed energy loss of up to 50 percent of the original energy.

Photochemical electron transfer at fixed distance : a synthetic model of the photosynthetic primary process

A series of meso-phenyloctamethylporphyrins covalently bonded at the 4'phenyl position to quinones via rigid bicyclo[2.2.2]octane spacers were synthesized for the study of the dependence of electron transfer reaction rate on solvent, distance, temperature, and energy gap. A general and convergent synthesis was developed based on the condensation of ac-biladienes with masked quinonespacer-benzaldehydes. From picosecond fluorescence spectroscopy emission lifetimes were measured in seven solvents of varying polarity. Rate constants were determined to vary from 5.0x10⁹sec^-1 in N,N-dimethylformamide to 1.15x10¹⁰ Sec^-1 in benzene, and were observed to rise at most by about a factor of three with decreasing solvent polarity. Experiments at low temperature in 2-MTHF glass (77K) revealed fast, nearly temperature-independent electron transfer characterized by non-exponential fluorescence decays, in contrast to monophasic behavior in fluid solution at 298K. This example evidently represents the first photosynthetic model system not based on proteins to display nearly temperature-independent electron transfer at high temperatures (nuclear tunneling). Low temperatures appear to freeze out the rotational motion of the chromophores, and the observed nonexponential fluorescence decays may be explained as a result of electron transfer from an ensemble of rotational conformations. The nonexponentiality demonstrates the sensitivity of the electron transfer rate to the precise magnitude of the electronic matrix element, which supports the expectation that electron transfer is nonadiabatic in this system. The addition of a second bicyclooctane moiety (15 Å vs. 18 Å edge-to-edge between porphyrin and quinone) reduces the transfer rate by at least a factor of 500-1500. Porphyrinquinones with variously substituted quinones allowed an examination of the dependence of the electron transfer rate constant κ_ET on reaction driving force. The classical trend of increasing rate versus increasing exothermicity occurs from 0.7 eV≤ |ΔG^0'(R)| ≤ 1.0 eV until a maximum is reached (κ_ET = 3 x 10⁸ sec^-1 rising to 1.15 x 10¹⁰ sec^-1 in acetonitrile). The rate remains insensitive to ΔG⁰ for ~ 300 mV from 1.0 eV≤ |ΔG^0’(R)| ≤ 1.3 eV, and then slightly decreases in the most exothermic case studied (cyanoquinone, κ_ET = 5 x 10⁹ sec^-1).