scholarly journals Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila

2018 ◽  
Vol 7 (5) ◽  
pp. 1359-1370 ◽  
Author(s):  
Anna B. Buchman ◽  
Tobin Ivy ◽  
John M. Marshall ◽  
Omar S. Akbari ◽  
Bruce A. Hay
Keyword(s):  
High Threshold ◽  
Population Replacement ◽  
Chromosome Translocations

scholarly journals Engineered reciprocal chromosome translocations drive high threshold, reversible population replacement in Drosophila

2016 ◽  
Author(s):  
Anna B. Buchman ◽  
Tobin Ivy ◽  
John M. Marshall ◽  
Omar S. Akbari ◽  
Bruce A. Hay
Keyword(s):  
High Threshold ◽  
Gene Drive ◽  
Chromosomal Breakage ◽  
Population Replacement ◽  
Migration Rates ◽  
Chromosome Translocations ◽  
Laboratory Populations ◽  
Insect Populations ◽  
And Migration ◽  
Global Population

AbstractReplacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions provides self-perpetuating methods of disease prevention and population suppression, respectively. Gene drive mechanisms that require the gene drive element and linked cargo exceed a high threshold frequency to spread are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold required for drive. It has long been recognized that reciprocal chromosome translocations could, in principal, be used to bring about high threshold gene drive through a form of underdominance. However, translocations able to drive population replacement have not been reported, leaving it unclear if translocation-bearing strains fit enough to mediate gene drive can easily be generated. Here we use modeling to identify a range of conditions under which translocations should spread, and the equilibrium frequencies achieved, given specific introduction frequencies, fitness costs and migration rates. We also report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. By several measures translocation-bearing strains are fit, and drive high threshold, reversible population replacement in laboratory populations. These observations, together with the generality of the tools used to generate translocations, suggest that engineered translocations may be useful for controlled population replacement in many species.

scholarly journals Gene Drives Across Engineered Fitness Valleys: Modeling a Design to Prevent Drive Spillover

2020 ◽  
Author(s):  
Frederik J.H. de Haas ◽  
Sarah P. Otto
Keyword(s):  
Local Population ◽  
Target Population ◽  
Drive System ◽  
High Threshold ◽  
Gene Drive ◽  
Time Model ◽  
Population Replacement ◽  
Low Threshold ◽  
Drive Systems ◽  
Gene Drives

1AbstractEngineered gene drive techniques for population replacement and/or suppression have potential for tackling complex challenges, including reducing the spread of diseases and invasive species. Unfortunately, the self-propelled behavior of drives can lead to the spread of transgenic elements beyond the target population, which is concerning. Gene drive systems with a low threshold frequency for invasion, such as homing-based gene drive systems, require initially few transgenic individuals to spread and are therefore easy to implement. However their ease of spread presents a double-edged sword; their low threshold makes these drives much more susceptible to spread outside of the target population (spillover). We model a proposed drive system that transitions in time from a low threshold drive system (homing-based gene drive) to a high threshold drive system (underdominance) using daisy chain technology. This combination leads to a spatially restricted drive strategy, while maintaining an attainable release threshold. We develop and analyze a discrete-time model as proof of concept and find that this technique effectively generates stable local population suppression, while preventing the spread of transgenic elements beyond the target population under biologically realistic parameters.

Conscious access to fear-relevant information is mediated by threshold

2011 ◽  
Vol 42 (2) ◽  
pp. 56-64 ◽  
Author(s):  
Remigiusz Szczepanowski
Keyword(s):  
Present Report ◽  
Intrinsic Property ◽  
Roc Curves ◽  
Relevant Information ◽  
Perceptual Processing ◽  
High Threshold ◽  
Operating Characteristics ◽  
Emotional Perception ◽  
Fearful Faces ◽  
The Subject

Conscious access to fear-relevant information is mediated by thresholdThe present report proposed a model of access consciousness to fear-relevant information according to which there is a threshold for emotional perception beyond that the subject makes hits with no false alarm. The model was examined by having the participants performed a confidence-ratings masking task with fearful faces. Measures of the thresholds for conscious access were taken by looking at the receiver operating characteristics (ROC) curves generated from a three-state low- and high-threshold (3-LHT) model by Krantz. Indeed, the analysis of the masking data revealed that the ROCs had threshold-like-nature (a two-limb shape) rather continuous (a curvilinear shape) challenging in this fashion the classical signal-detection view on perceptual processing. Moreover, the threshold ROC curve exhibited the specific y-intercepts relevant to conscious access performance. The study suggests that the threshold can be an intrinsic property of conscious access, mediating emotional contents between perceptual states and consciousness.

A New Look at the Asian Fertility Transition (Distinguishedl Lecture)

1996 ◽  
Vol 35 (4I) ◽  
pp. 385-398 ◽  
Author(s):  
John C. Caldwell
Keyword(s):  
Total Fertility Rate ◽  
Birth Rate ◽  
Fertility Transition ◽  
Fertility Rate ◽  
Asian Women ◽  
Population Replacement ◽  
Planning Meeting ◽  
Annual Birth Rate

The significance of the Asian fertility transition can hardly be overestimated. The relatively sanguine view of population growth expressed at the 1994 International Conference for Population and Development (ICPD) in Cairo was possible only because of the demographic events in Asia over the last 30 years. In 1965 Asian women were still bearing about six children. Even at current rates, today’s young women will give birth to half as many. This measure, namely the average number of live births over a reproductive lifetime, is called the total fertility rate. It has to be above 2— considerably above if mortality is still high—to achieve long-term population replacement. By 1995 East Asia, taken as a whole, exhibited a total fertility rate of 1.9. Elsewhere, Singapore was below long-term replacement, Thailand had just achieved it, and Sri Lanka was only a little above. The role of Asia in the global fertility transition is shown by estimates I made a few years ago for a World Bank Planning Meeting covering the first quarter of a century of the Asian transition [Caldwell (1993), p. 300]. Between 1965 and 1988 the world’s annual birth rate fell by 22 percent. In 1988 there would have been 40 million more births if there had been no decline from 1965 fertility levels. Of that total decline in the world’s births, almost 80 percent had been contributed by Asia, compared with only 10 percent by Latin America, nothing by Africa, and, unexpectedly, 10 percent by the high-income countries of the West. Indeed, 60 percent of the decline was produced by two countries, China and India, even though they constitute only 38 percent of the world’s population. They accounted, between them, for over threequarters of Asia’s fall in births.

scholarly journals Rapid Multi-Hybridisation FISH Screening for Balanced Porcine Reciprocal Translocations Suggests a Much Higher Abnormality Rate Than Previously Appreciated

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 250
Author(s):  
Rebecca E O’Connor ◽  
Lucas G Kiazim ◽  
Claudia C Rathje ◽  
Rebecca L Jennings ◽  
Darren K Griffin
Keyword(s):  
Semen Analysis ◽  
In Situ Hybridisation ◽  
Economic Loss ◽  
Environmental Damage ◽  
Fluorescence In Situ Hybridisation ◽  
Reciprocal Translocations ◽  
Chromosome Translocations ◽  
Farrowing Rate ◽  
Significant Economic Loss

With demand rising, pigs are the world’s leading source of meat protein; however significant economic loss and environmental damage can be incurred if boars used for artificial insemination (AI) are hypoprolific (sub-fertile). Growing evidence suggests that semen analysis is an unreliable tool for diagnosing hypoprolificacy, with litter size and farrowing rate being more applicable. Once such data are available, however, any affected boar will have been in service for some time, with significant financial and environmental losses incurred. Reciprocal translocations (RTs) are the leading cause of porcine hypoprolificacy, reportedly present in 0.47% of AI boars. Traditional standard karyotyping, however, relies on animal specific expertise and does not detect more subtle (cryptic) translocations. Previously, we reported development of a multiple hybridisation fluorescence in situ hybridisation (FISH) strategy; here, we report on its use in 1641 AI boars. A total of 15 different RTs were identified in 69 boars, with four further animals XX/XY chimeric. Therefore, 4.5% had a chromosome abnormality (4.2% with an RT), a 0.88% incidence. Revisiting cases with both karyotype and FISH information, we reanalysed captured images, asking whether the translocation was detectable by karyotyping alone. The results suggest that chromosome translocations in boars may be significantly under-reported, thereby highlighting the need for pre-emptive screening by this method before a boar enters a breeding programme.

scholarly journals A model of on/off transitions in neurons of the deep cerebellar nuclei: deciphering the underlying ionic mechanisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hugues Berry ◽  
Stéphane Genet
Keyword(s):  
Cerebellar Nuclei ◽  
Biophysical Model ◽  
High Threshold ◽  
Deep Cerebellar Nuclei ◽  
Functional Link ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
The Central Nervous System ◽  
Overall Functioning

AbstractThe neurons of the deep cerebellar nuclei (DCNn) represent the main functional link between the cerebellar cortex and the rest of the central nervous system. Therefore, understanding the electrophysiological properties of DCNn is of fundamental importance to understand the overall functioning of the cerebellum. Experimental data suggest that DCNn can reversibly switch between two states: the firing of spikes (F state) and a stable depolarized state (SD state). We introduce a new biophysical model of the DCNn membrane electro-responsiveness to investigate how the interplay between the documented conductances identified in DCNn give rise to these states. In the model, the F state emerges as an isola of limit cycles, i.e. a closed loop of periodic solutions disconnected from the branch of SD fixed points. This bifurcation structure endows the model with the ability to reproduce the $\text{F}\to \text{SD}$ F → SD transition triggered by hyperpolarizing current pulses. The model also reproduces the $\text{F}\to \text{SD}$ F → SD transition induced by blocking Ca currents and ascribes this transition to the blocking of the high-threshold Ca current. The model suggests that intracellular current injections can trigger fully reversible $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. Investigation of low-dimension reduced models suggests that the voltage-dependent Na current is prominent for these dynamical features. Finally, simulations of the model suggest that physiological synaptic inputs may trigger $\text{F}\leftrightarrow \text{SD}$ F ↔ SD transitions. These transitions could explain the puzzling observation of positively correlated activities of connected Purkinje cells and DCNn despite the former inhibit the latter.

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