Multistep allelic conversion in mouse pre-implantation embryos by AAV vectors.

Site-specific recombinases (SSRs) are critical for achieving precise spatiotemporal control of engineered alleles. These enzymes play a key role in facilitating the deletion or inversion of loci flanked by recombination sites, resulting in the activation or repression of endogenous genes, selection markers or reporter elements. However, multiple recombination in complex alleles can be laborious.

The role of the Bemisia tabaci and Trialeurodes vaporariorum cytochrome-P450 clade CYP6DPx in resistance to nicotine and neonicotinoids.

The alkaloid, nicotine, produced by tobacco and other Solanaceae as an anti-herbivore defence chemical is one of the most toxic natural insecticides in nature. However, some insects, such as the whitefly species, Trialeurodes vaporariorum and Bemisia tabaci show strong tolerance to this allelochemical and can utilise tobacco as a host. Here, we used biological, molecular and functional approaches to investigate the role of cytochrome P450 enzymes in nicotine tolerance in T.

Characterization of emamectin benzoate resistance in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

Background: Plutella xylostella (L.) is a destructive pest of cruciferous crops worldwide that has evolved resistance to many insecticides. Here we examined the mode of inheritance, cross-resistance profile, and potential mechanisms of emamectin benzoate resistance in a field-derived strain of P.

The Potential Roles of Transacylation in Intracellular Lipolysis and Related Qssa Approximations.

Fatty acids (FAs) are crucial energy metabolites, signalling molecules, and membrane building blocks for a wide range of organisms. Adipose triglyceride lipase (ATGL) is the first and presumingly most crucial regulator of FA release from triacylglycerols (TGs) stored within cytosolic lipid droplets. However, besides the function of releasing FAs by hydrolysing TGs into diacylglycerols (DGs), ATGL also promotes the transacylation reaction of two DG molecules into one TG and one monoacylglycerol molecule.

Frequency and spatial distribution of knock-down resistance (kdr) to pyrethroids in multiple oilseed rape pest species of the genus Ceutorhynchus.

Background: The protection of European oilseed rape (OSR) from damaging insects relies on pyrethroid insecticides, but the development of resistance in key coleopteran pests such as the pollen beetle (Brassicogethes aeneus) and the cabbage stem flea beetle (Psylliodes chrysocephala) has resulted in reduced effectiveness of these insecticides. The sodium channel gene mutation L1014F knock-down resistance (kdr) is a contributing factor in resistance to pyrethroids in B. aeneus and P.

A single point mutation in the Bemisia tabaci cytochrome-P450 CYP6CM1 causes enhanced resistance to neonicotinoids.

The tobacco whitefly, Bemisia tabaci, is a polyphagous crop pest which causes high levels of economic damage across the globe. Insecticides are often required for the effective control of this species, among which the neonicotinoid class have been particularly widely used. Deciphering the mechanisms responsible for resistance to these chemicals is therefore critical to maintain control of B.

An aggregation model of cockroaches with fast-or-slow motion dichotomy.

We propose a mathematical model, namely a reaction-diffusion system, to describe social behaviour of cockroaches. An essential new aspect in our model is that the dispersion behaviour due to overcrowding effect is taken into account as a counterpart to commonly studied aggregation. This consideration leads to an intriguing new phenomenon which has not been observed in the literature.

Structural Biology-Guided Design, Synthesis, and Biological Evaluation of Novel Insect Nicotinic Acetylcholine Receptor Orthosteric Modulators.

The development of novel and safe insecticides remains an important need for a growing world population to protect crops and animal and human health. New chemotypes modulating the insect nicotinic acetylcholine receptors have been recently brought to the agricultural market, yet with limited understanding of their molecular interactions at their target receptor. Herein, we disclose the first crystal structures of these insecticides, namely, sulfoxaflor, flupyradifurone, triflumezopyrim, flupyrimin, and the experimental compound, dicloromezotiaz, in a double-mutated acetylcholine-binding protein which mimics the insect-ion-channel orthosteric site.

Mathematical Modelling of p53 Signalling during DNA Damage Response: A Survey.

No gene has garnered more interest than p53 since its discovery over 40 years ago. In the last two decades, thanks to seminal work from Uri Alon and Ghalit Lahav, p53 has defined a truly synergistic topic in the field of mathematical biology, with a rich body of research connecting mathematic endeavour with experimental design and data. In this review we survey and distill the extensive literature of mathematical models of p53.

Investigating the status of pyrethroid resistance in UK populations of the cabbage stem flea beetle ().

The cabbage stem flea beetle, L. is a major pest of winter oilseed rape in several European countries. Traditionally, neonicotinoid and pyrethroid insecticides have been widely used for control of , but in recent years, following the withdrawal of neonicotinoid insecticide seed treatments, control failures have occurred due to an over reliance on pyrethroids.

Efficient allele conversion in mouse zygotes and primary cells based on electroporation of Cre protein.

Cre-loxP recombination system is a powerful tool for genome engineering. One of its applications is found in genetic mouse models that often require to induce Cre recombination in preimplantation embryos. Here, we describe a technically simple, affordable and highly efficient protocol for Cre protein delivery into mouse zygotes by electroporation.

Host plant adaptation in the polyphagous whitefly, Trialeurodes vaporariorum, is associated with transcriptional plasticity and altered sensitivity to insecticides.

Background: The glasshouse whitefly, Trialeurodes vaporariorum, is a damaging crop pest and an invasive generalist capable of feeding on a broad range of host plants. As such this species has evolved mechanisms to circumvent the wide spectrum of anti-herbivore allelochemicals produced by its host range. T.

TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting subunit c incorporation into the rotor structure of the enzyme.

Biogenesis of FF ATP synthase, the key enzyme of mitochondrial energy provision, depends on transmembrane protein 70 (TMEM70), localized in the inner mitochondrial membrane of higher eukaryotes. TMEM70 absence causes severe ATP-synthase deficiency and leads to a neonatal mitochondrial encephalocardiomyopathy in humans. However, the exact biochemical function of TMEM70 remains unknown.

A flavin-dependent monooxgenase confers resistance to chlorantraniliprole in the diamondback moth, Plutella xylostella.

The diamondback moth, Plutella xylostella, is a damaging pest of cruciferous crops, and has evolved resistance to many of the insecticides used for control, including members of the diamide class. Previous work on the molecular basis of resistance to diamides has documented mutations in the target-site, the ryanodine receptor, in resistant populations of P. xylostella worldwide.

Trend to Equilibrium for a Reaction-Diffusion System Modelling Reversible Enzyme Reaction.

A spatio-temporal evolution of chemicals appearing in a reversible enzyme reaction and modelled by a four-component reaction-diffusion system with the reaction terms obtained by the law of mass action is considered. The large time behaviour of the system is studied by means of entropy methods.

Boundary Layer Effect on Behavior of Discrete Models.

The paper studies systems of rigid bodies with randomly generated geometry interconnected by normal and tangential bonds. The stiffness of these bonds determines the macroscopic elastic modulus while the macroscopic Poisson's ratio of the system is determined solely by the normal/tangential stiffness ratio. Discrete models with no directional bias have the same probability of element orientation for any direction and therefore the same mechanical properties in a statistical sense at any point and direction.

Positive effect of Mdm2 on p53 expression explains excitability of p53 in response to DNA damage.

Most of the existing biological models consider Mdm2 as a dominant negative regulator of p53 appearing in several negative feedback loops. However, in addition to targeting p53 for degradation, Mdm2 in tight cooperation with MdmX can control expression levels of p53 through enhanced induction of p53 synthesis in response to DNA damage. Whilst ATM-dependent phosphorylation of p53 is not observed to be important in this enhanced synthesis, ATM-dependent phosphorylation of Mdm2 (as well as MdmX) is essential for its dual role, which is accompanied with widely oscillating p53.

Biochemical and Molecular Mechanisms Associated With the Resistance of the European Corn Borer (Lepidoptera: Crambidae) to Lambda-Cyhalothrin and First Monitoring Tool.

The European corn borer (Ostrinia nubilalis (Hübner)) is one of the most serious corn pest in Europe where it is controlled with pesticides, in particular, pyrethroids. First control failures with this chemical family occurred on the field in 2008 in the center of France, and the first resistance case was described in 2012. In the present study, we investigate resistance mechanisms involved in seven French populations of O.

Use of an individual-based simulation model to explore and evaluate potential insecticide resistance management strategies.

Background: Tools with the potential to predict risks of insecticide resistance and aid the evaluation and design of resistance management tactics are of value to all sectors of the pest management community. Here we describe use of a versatile individual-based model of resistance evolution to simulate how strategies employing single and multiple insecticides influence resistance development in the pollen beetle, Meligethes aeneus.

Results: Under repeated exposure to a single insecticide, resistance evolved faster to a pyrethroid (lambda-cyhalothrin) than to a pyridine azomethane (pymetrozine), due to difference in initial efficacy.

An individual-based model of the evolution of pesticide resistance in heterogeneous environments: control of Meligethes aeneus population in oilseed rape crops.

Preventing a pest population from damaging an agricultural crop and, at the same time, preventing the development of pesticide resistance is a major challenge in crop protection. Understanding how farming practices and environmental factors interact with pest characteristics to influence the spread of resistance is a difficult and complex task. It is extremely challenging to investigate such interactions experimentally at realistic spatial and temporal scales.

Reaction-diffusion systems for spatio-temporal intracellular protein networks: A beginner's guide with two examples.

Spatio-temporal dynamics of a variety of proteins is, among other things, regulated by post-translational modifications of these proteins. Such modifications can thus influence stability and biochemical activities of the proteins, activity and stability of their upstream targets within specific signalling pathways. Commonly used mathematical tools for such protein-protein (and/or protein-mRNA) interactions in single cells, namely, Michaelis-Menten and Hill kinetics, yielding a system of ordinary differential equations, are extended here into (non-linear) partial differential equations by taking into account a more realistic spatial representation of the environment where these reactions occur.

The dynamics of p53 in single cells: physiologically based ODE and reaction-diffusion PDE models.

The intracellular signalling network of the p53 protein plays important roles in genome protection and the control of cell cycle phase transitions. Recently observed oscillatory behaviour in single cells under stress conditions has inspired several research groups to simulate and study the dynamics of the protein with the aim of gaining a proper understanding of the physiological meanings of the oscillations. We propose compartmental ODE and PDE models of p53 activation and regulation in single cells following DNA damage and we show that the p53 oscillations can be retrieved by plainly involving p53-Mdm2 and ATM-p53-Wip1 negative feedbacks, which are sufficient for oscillations experimentally, with no further need to introduce any delays into the protein responses and without considering additional positive feedback.