Continuing field efficacy of norbormide against both Rattus rattus (ship rats) and Rattus norvegicus (Norway rats)

Norbormide is a uniquely selective rat toxicant for Rattus species, with rats being 100- to 150-fold more sensitive to norbormide toxicity than most other mammals and birds. Previously we reported that on completion of a 10-year program of targeted fundamental and applied synthetic chemistry and toxicology, taste aversion associated with this compound had been overcome. In 2020-2022, trials have been successfully completed on poultry farms with Norway rats and larger scale field trials were undertaken targeting ship rats using 1% norbormide paste baits. Firstly, the efficacy of norbormide-containing paste baits targeting rat infestations on poultry farms was proven with a 100% reduction of Norway rat populations on three different farms. Secondly, 100% reduction in ship rat abundance was achieved at two large field test sites; and no reduction was achieved at the untreated control site. These larger field trials are described in depth in this publication. Plans are progressing to complete product development and registration

Magnetorheological landing gear: 2. Validation using experimental data

Aircraft landing gears are subjected to a wide range of excitation conditions with conflicting damping requirements. A novel solution to this problem is to implement semi-active damping using magnetorheological (MR) fluids. In part 1 of this contribution, a methodology was developed that enables the geometry of a flow mode MR valve to be optimized within the constraints of an existing passive landing gear. The device was designed to be optimal in terms of its impact performance, which was demonstrated using numerical simulations of the complete landing gear system. To perform the simulations, assumptions were made regarding some of the parameters used in the MR shock strut model. In particular, the MR fluid's yield stress, viscosity, and bulk modulus properties were not known accurately. Therefore, the present contribution aims to validate these parameters experimentally, via the manufacture and testing of an MR shock strut. The gas exponent, which is used to model the shock strut's nonlinear stiffness, is also investigated. In general, it is shown that MR fluid property data at high shear rates are required in order to accurately predict performance prior to device manufacture. Furthermore, the study illustrates how fluid compressibility can have a significant influence on the device time constant, and hence on potential control strategies

Mandated data archiving greatly improves access to research data

The data underlying scientific papers should be accessible to researchers both now and in the future, but how best can we ensure that these data are available? Here we examine the effectiveness of four approaches to data archiving: no stated archiving policy, recommending (but not requiring) archiving, and two versions of mandating data deposition at acceptance. We control for differences between data types by trying to obtain data from papers that use a single, widespread population genetic analysis, STRUCTURE. At one extreme, we found that mandated data archiving policies that require the inclusion of a data availability statement in the manuscript improve the odds of finding the data online almost a thousand-fold compared to having no policy. However, archiving rates at journals with less stringent policies were only very slightly higher than those with no policy at all. At one extreme, we found that mandated data archiving policies that require the inclusion of a data availability statement in the manuscript improve the odds of finding the data online almost a thousand fold compared to having no policy. However, archiving rates at journals with less stringent policies were only very slightly higher than those with no policy at all. We also assessed the effectiveness of asking for data directly from authors and obtained over half of the requested datasets, albeit with about 8 days delay and some disagreement with authors. Given the long term benefits of data accessibility to the academic community, we believe that journal based mandatory data archiving policies and mandatory data availability statements should be more widely adopted

Transcriptomics-Based Network Medicine Approach Identifies Metformin as a Repurposable Drug for Atrial Fibrillation

Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. This study demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug tar-gets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF. Using the active compactor, a new design analysis of large-scale longitudinal electronic health record (EHR) data, we determine that metformin use is significantly associated with a reduced risk of AF (odds ratio = 0.48, 95%, confidence interval [CI] 0.36- 0.64, p \u3c 0.001) compared with standard treatments for diabetes. This study utilizes network medicine meth-odologies to identify repurposed drugs for AF treatment and identifies metformin as a candidate drug

Retrieving and retaining older and advancing novel rodenticides-as alternatives to anticoagulants

Eason, C.T., Henderson, R., Murphy, E., Shapiro, L., MacMorran, D., Blackie, H., Brimble, M., Conole, D., Rennison, D., Gibson, T.J., Gregory N.G

Milk yield estimation during suckling using the double oxytocin injection-milking and the double weighing-suckling methods in dairy goats

The aim was to verify the validity of the double oxytocin-milking (DOT) method as milk yield estimator during the suckling period of lactating dairy goats. To this end, it was necessary to determine whether the weighing suckling weighing (WSW) and DOT methods of milk yield estimation satisfied the criteria to be considered valuable, the accuracy between both methods and the suitability of DOT to evaluate actual milk. At parturition, sixty lactating Murciano Granadina breed goats were separated into 2 groups, in mixed (MS; n = 24) and artificial rearing (ARS; n = 36) management systems. Until the sixth week of lactation (weaning), MS goats suckled one kid while kids from ARS goats were artificially reared; moreover, goats in both systems were submitted to once-a-day milking. Once per week, actual milk yield for ARS goats and potential milk yield were recorded using DOT method for all goats, except for 12 goats in ARS which remained as a control. Twelve goats from each management system were used to evaluate diurnal variation in milk production (DVM) by DOT method for 6 consecutive days in week 4 of lactation. No difference in DVM was found by DOT method in 4-h milk production of goats in MS (P = 0.099) or ARS (P = 0.220), which allowed sixfold multiplication of milked milk volume to obtain potential milk per day. ARS goats subjected to a weekly DOT and control group goats showed a similar (P = 0.379) lactation curve for the first 6 weeks of lactation. The DOT method slightly overestimated (3.4%, P = 0.005) the milk yield evaluated by WSW method for goats under an MS, but fitted the actual milk obtained by common milk records for the group of goats in an ARS submitted to the DVM test (P = 0.357) and the group in ARS alone (P = 0.163). The DOT method applied for 8 consecutive days led to a drop of 6 12% in milk yield during the following week for both production systems. In conclusion, DOT was an accurate method to estimate milk yield during the first weeks of lactation both in MS and ARS under the conditions of this experiment. © 2013 Elsevier B.V. All rights reserved.Fernández Martínez, N.; Balasch Parisi, S.; Pérez Baena, I.; Rodríguez Garcia, M.; Peris Ribera, CJ. (2013). Milk yield estimation during suckling using the double oxytocin injection-milking and the double weighing-suckling methods in dairy goats. Small Ruminant Research. 112(1-3):181-185. doi:10.1016/j.smallrumres.2012.12.023S1811851121-

Effects of urban-induced mutations on ecology, evolution and health

Increasing evidence suggests that urbanization is associated with higher mutation rates, which can affect the health and evolution of organisms that inhabit cities. Elevated pollution levels in urban areas can induce DNA damage, leading to de novo mutations. Studies on mutations induced by urban pollution are most prevalent in humans and microorganisms, whereas studies of non-human eukaryotes are rare, even though increased mutation rates have the potential to affect organisms and their populations in contemporary time. Our Perspective explores how higher mutation rates in urban environments could impact the fitness, ecology and evolution of populations. Most mutations will be neutral or deleterious, and higher mutation rates associated with elevated pollution in urban populations can increase the risk of cancer in humans and potentially other species. We highlight the potential for urban-driven increased deleterious mutational loads in some organisms, which could lead to a decline in population growth of a wide diversity of organisms. Although beneficial mutations are expected to be rare, we argue that higher mutation rates in urban areas could influence adaptive evolution, especially in organisms with short generation times. Finally, we explore avenues for future research to better understand the effects of urban-induced mutations on the fitness, ecology and evolution of city-dwelling organisms

Eda haplotypes in three-spined stickleback are associated with variation in immune gene expression

Haplotypes underlying local adaptation and speciation are predicted to have numerous phenotypic effects, but few genes involved have been identified, with much work to date concentrating on visible, morphological, phenotypes. The link between genes controlling these adaptive morphological phenotypes and the immune system has seldom been investigated, even though changes in the immune system could have profound adaptive consequences. The Eda gene in three-spined stickleback is one of the best studied major adaptation genes; it directly controls bony plate architecture and has been associated with additional aspects of adaptation to freshwater. Here, we exposed F2 hybrids, used to separate Eda genotype from genetic background, to contrasting conditions in semi-natural enclosures. We demonstrate an association between the Eda haplotype block and the expression pattern of key immune system genes. Furthermore, low plated fish grew less and experienced higher burdens of a common ectoparasite with fitness consequences. Little is currently known about the role of the immune system in facilitating adaptation to novel environments, but this study provides an indication of its potential importance

A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart

Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory chow (7% kcal from fat) for 3 weeks, after which we measured cardiac function in vivo using cine MRI, efficiency in isolated working hearts and respiration rates and ADP/O ratios in isolated interfibrillar mitochondria; also, measured were medium chain acyl-CoA dehydrogenase (MCAD) and citrate synthase activities plus uncoupling protein 3 (UCP3), mitochondrial thioesterase 1 (MTE-1), adenine nucleotide translocase (ANT) and ATP synthase protein levels. We found that in vivo cardiac function was the same for all rats, yet oxygen consumption was 19% higher in high fat-fed rat hearts, therefore, efficiency was 21% lower than in controls. We found that mitochondrial fatty acid oxidation rates were 25% higher, and MCAD activity was 23% higher, in hearts from rats fed the high fat diet when compared with controls. Mitochondria from high fat-fed rat hearts had lower ADP/O ratios than controls, indicating increased respiratory uncoupling, which was ameliorated by GDP, a UCP3 inhibitor. Mitochondrial UCP3 and MTE-1 levels were both increased by 20% in high fat-fed rat hearts when compared with controls, with no significant change in ATP synthase or ANT levels, or citrate synthase activity. We conclude that increased cardiac oxygen utilisation, and thereby decreased cardiac efficiency, occurs in non-genetic obesity, which is associated with increased mitochondrial uncoupling due to elevated UCP3 and MTE-1 levels