Chapter 9 Gene Drive Strategies for Population Replacement

Gene drive systems are selfish genetic elements capable of spreading into a population despite a fitness cost. A variety of these systems have been proposed for spreading disease-refractory genes into mosquito populations, thus reducing their ability to transmit diseases such as malaria and dengue fever to humans. Some have also been proposed for suppressing mosquito populations. We assess the alignment of these systems with design criteria for their safety and efficacy. Systems such as homing endonuclease genes, which manipulate inheritance through DNA cleavage and repair, are highly invasive and well-suited to population suppression efforts. Systems such as Medea, which use combinations of toxins and antidotes to favor their own inheritance, are highly stable and suitable for replacing mosquito populations with disease-refractory varieties. These systems offer much promise for future vector-borne disease control

Iridium-coated rhenium thrusters by CVD

Operation of spacecraft thrusters at increased temperature reduces propellant requirements. Inasmuch as propellant comprises the bulk of a satellite's mass, even a small percentage reduction makes possible a significant enhancement of the mission in terms of increased payload. Because of its excellent high temperature strength, rhenium is often the structural material of choice. It can be fabricated into free-standing shapes by chemical vapor deposition (CVD) onto an expendable mandrel. What rhenium lacks is oxidation resistance, but this can be provided by a coating of iridium, also by CVD. This paper describes the process used by Ultramet to fabricate 22-N (5-lbf) and, more recently, 445-N (100-lbf) Ir/Re thrusters; characterizes the CVD-deposited materials; and summarizes the materials effects of firing these thrusters. Optimal propellant mixture ratios can be employed because the materials withstand an oxidizing environment up to the meltimg temperature of iridium, 2400 C (4350 F)

Property Insurance with Conversion Options: Upper Limits and Deductibles

The paper compares models of insurance of real property when owners may convert damaged property to another use instead of restoring it to the pre-damage use. First it describes the optimum insurance. The main result is that the deductible and the upper limit are connected by the equation: upper limit plus deductible equals conversion point. An alternative to the full optimum is a policy having a variable upper limit and a fixed deductible. It is interesting for theoretical reasons and for descriptive reality. The comparative statics of the full optimum and the fixed-deductible alternative are essentially the same. In the fixed-deductible model, the response of the upper limit to changes in parameters is always in the same direction but of lesser magnitude than in the full optimum.

Pmp27 Promotes Peroxisomal Proliferation

Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Prop27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of β-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission.

General principles of single-construct chromosomal gene drive

Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of offspring arising from specific parental crosses unviable. Under permissive conditions, a number of these elements are capable of distorting the offspring ratio in their favor. We use a population genetic framework to derive conditions under which these elements spread to fixation in a population or induce a population crash. Many of these systems can be engineered using combinations of toxin and antidote genes, analogous to Medea, which consists of a maternal toxin and zygotic antidote. The majority of toxin–antidote drive systems require a critical frequency to be exceeded before they spread into a population. Of particular interest, a Z-linked Medea construct with a recessive antidote is expected to induce an all-male population crash for release frequencies above 50%. We suggest molecular tools that may be used to build these systems, and discuss their relevance to the control of a variety of insect pest species, including mosquito vectors of diseases such as malaria and dengue fever

Multi-Laboratory Results for the Cathodoluminescence Emission Spectrum from a Synthetic Zircon Standard

The Standards Committee of the Society for Luminescence Microscopy and Spectroscopy (SLMS) circulated doped zircon crystals as a standard for comparison of cathodoluminescence (CL) emission spectra obtained at different laboratories. Eleven laboratories have submitted spectra acquired from this standard. The crystals are synthetic zircons doped with 1.4 wt.% of Dy2O3 The participating laboratories used a variety of CL instrumentation including cold cathode optical micro-scope attachments, hot cathode optical microscope attachments, and EMPA/SEM-based systems. Two laboratories provided both uncorrected and corrected spectra. All other spectra are uncorrected. A variety of different spectrometers/spectrographs and detector systems were used. Photomultiplier tubes (PMTs), photo diode arrays, intensified photo diode arrays, and charge coupled devices (CCDs) are represented among the final results. The laboratories with apparently the best resolving power reported 8 peaks in the multiplet at 485 nm. The spectra submitted by some laboratories showed only a single peak at this position. The wavelength scale calibrations were compared by noting the wavelength of the most intense peak in the 485 multiplet. This varied from 476.3 nm to 489 nm among the eleven laboratories. The systems have different overall transmission and detection functions: a combination of the influence of the transmission of the viewing window (typically leaded-glass), the microscope, the fiber optics coupling (if used), the response of the grating and spectrometer/spectrograph, and the detector response. As an initial test of this variation, the ratio of the peak maximum intensity at 575 nm to that at 485 nm was compared. This ratio varied from 0.6 to 3.93 among the eleven laboratories