Controlling invasive rodents via synthetic gene drive and the role of polyandry

House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male’s sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three- to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design

The influence of different footprint preparation techniques on tissue regeneration in rotator cuff repair in an animal model

Introduction: Rotator cuff tears are common diseases of the upper extremity. There are no recommendations to the surgeon on how to prepare the footprint to ensure optimal tendon-to-bone healing. However, biologic augmentation using stem cells and growth factors is considered to encourage the healing process of the tendon. The aim of the study was to investigate the biomechanical and histological outcome of different footprint preparations in rotator cuff repair. Material and methods: One hundred and eighty-nine Sprague-Dawley rats were randomly assigned to either spongialization, radiofrequency ablation or an untreated control group. Rats were killed after 1 or 7 weeks for histological evaluation or after 7 weeks for biomechanical testing. Results: Histological evaluation showed better tissue organization in the control and spongialization group compared to the radiofrequency ablation group. The highest collagen I to collagen III quotient was found in the control group, followed closely by the spongialization group. Measured quotients showed a decrease in the values after 1 week compared to the values after 7 weeks, except in the radiofrequency ablation group, where an increase was detected. A significant difference was found in the load to failure test comparing the radiofrequency ablation group to the spongialization group (p = 0.0409) and control group (p = 0.014), but not comparing the spongialization group to the control group (p = 0.2456). Conclusions: The results of this study suggest that spongialization of the footprint before attaching the torn supraspinatus tendon can lead to better structural properties and higher quality of tendon-to-bone restoration at the insertion area when compared with radiofrequency ablation

Synthesis and characterisation of ruthenium complexes containing a pendent catechol ring

A series of [Ru(bipy)₂L]⁺ and [Ru(phen)₂L]⁺ complexes where L is 2-[5-(3,4-dimethoxyphenyl)-4H-1,2,4-triazol-3-yl]pyridine (HL1) and 4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)benzene-1,2-diol (HL2) are reported. The compounds obtained have been characterised using X-ray crystallography, NMR, UV/Vis and emission spectroscopies. Partial deuteriation is used to determine the nature of the emitting state and to simplify the NMR spectra. The acid-base properties of the compounds are also investigated. The electronic structures of [Ru(bipy)₂L1]⁺ and Ru(bipy)₂HL1]²⁺ are examined using ZINDO. Electro and spectroelectrochemical studies on [Ru(bipy)₂(L2)]⁺ suggest that proton transfer between the catechol and triazole moieties on L2 takes place upon oxidation of the L2 ligand

German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Pseudomonas aeruginosa Isolates Using a Commercially Available Broth Microdilution Assay

Multidrug resistance is an emerging healthcare issue, especially concerning Pseudomonas aeruginosa. In this multicenter study, P. aeruginosa isolates with resistance against meropenem detected by routine methods were collected and tested for carbapenemase production and susceptibility against ceftazidime-avibactam. Meropenem-resistant isolates of P. aeruginosa from various clinical materials were collected at 11 tertiary care hospitals in Germany from 2017–2019. Minimum inhibitory concentrations (MICs) were determined via microdilution plates (MICRONAUT-S) of ceftazidime-avibactam and meropenem at each center. Detection of the presence of carbapenemases was performed by PCR or immunochromatography. For meropenem-resistant isolates (n = 448), the MIC range of ceftazidime-avibactam was 0.25–128 mg/L, MIC90 was 128 mg/L and MIC50 was 16 mg/L. According to EUCAST clinical breakpoints, 213 of all meropenem-resistant P. aeruginosa isolates were categorized as susceptible (47.5%) to ceftazidime-avibactam. Metallo-β-lactamases (MBL) could be detected in 122 isolates (27.3%). The MIC range of ceftazidime-avibactam in MBL-positive isolates was 4–128 mg/L, MIC90 was >128 mg/L and MIC50 was 32 mg/L. There was strong variation in the prevalence of MBL-positive isolates among centers. Our in vitro results support ceftazidimeavibactam as a treatment option against infections caused by meropenem-resistant, MBL-negative P. aeruginosa

Convoluting UV-Vis spectra using oscillator strengths

We describe the derivation of a formula to convolute UV-Visible spectra using (computed) oscillator strengths

R Source Code of the Model

This file contains the R Source Code of the most complex model (as described in Supplementary Text S4) investigating the ecology and evolution of the tSry gene when released into a population

Maple Code for Analytical Approximations

Contains the Maple file (.mw) that calculates critical release thresholds using plausible approximations as described in Supplementary Text S3

Data from: Controlling invasive rodents via synthetic gene drive and the role of polyandry

House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations due to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm killing drivers are extremely damaging to a male's sperm competitive ability. Here we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased 3- to 6-fold for successful eradication. We discuss the implications of our finding for pest potential control programs, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting are key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design

Maple Code for Analytical Approximations (.txt)

Contains the Maple code that calculates critical release thresholds using plausible approximations as described in Supplementary Text S3, in this version in a plain text (.txt)