Phenotype-Specific Semi-Mechanistic Modelling of Florfenicol Time-Kill Curves in G. Parasuis Compared to Other Respiratory Pathogens.

This study examines the pharmacodynamics (PD) of florfenicol (FFN) for treating porcine respiratory diseases by comparing its effects on Glaesserella parasuis, Actinobacillus pleuropneumoniae and Pasteurella multocida. In vitro time-kill assays and semi-mechanistic PD modeling were used to assess bacterial growth and killing rates at varying FFN concentrations. Species-specific PD models indicated that fAUC/MIC was the best PK/PD index across all species.

Hollow-fibre infection model: adaptations for the culture and assessment of fastidious organisms.

The hollow-fibre infection model (HFIM) is a valuable platform for emulating antimicrobial drug pharmacokinetic profiles. Despite its potential, standardized protocols for HFIM operation, especially concerning fastidious organisms, are lacking. This study addresses this gap by examining challenges in culturing and , two fastidious organisms, in the HFIM.

The differential assimilation of nitrogen fertilizer compounds by soil microorganisms.

The differential soil microbial assimilation of common nitrogen (N) fertilizer compounds into the soil organic N pool is revealed using novel compound-specific amino acid (AA) 15N-stable isotope probing. The incorporation of fertilizer 15N into individual AAs reflected the known biochemistry of N assimilation-e.g.

Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle.

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease.

Microplastics in human urine: Characterisation using μFTIR and sampling challenges using healthy donors and endometriosis participants.

Microplastics (MPs) are found in all environments, within the human food chain, and have been recently detected in several human tissues. The objective herein was to undertake an analysis of MP contamination in human urine samples, from healthy individuals and participants with endometriosis, with respect to their presence, levels, and the characteristics of any particles identified. A total of 38 human urine samples and 15 procedural blanks were analysed.

The mechanisms behind the contrasting responses to waterlogging in black-grass () and wheat ().

Black-grass (Alopecurus myosuroides ) is one of the most problematic agricultural weeds of Western Europe, causing significant yield losses in winter wheat (Triticum aestivum ) and other crops through competition for space and resources. Previous studies link black-grass patches to water-retaining soils, yet its specific adaptations to these conditions remain unclear. We designed pot-based waterlogging experiments to compare 13 biotypes of black-grass and six cultivars of wheat.

Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.

Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced corresponded with reduced SPMs.

CellShip: An Ambient Temperature Transport and Short-Term Storage Medium for Mammalian Cell Cultures.

Cell culture is a critical platform for numerous research and industrial processes. However, methods for transporting cells are largely limited to cryopreservation, which is logistically challenging, requires the use of potentially cytotoxic cryopreservatives, and can result in poor cell recovery. Development of a transport media that can be used at ambient temperatures would alleviate these issues.

Time-Kill Analysis of Canine Skin Pathogens: A Comparison of Pradofloxacin and Marbofloxacin.

Time-kill curves (TKCs) are more informative compared with the use of minimum inhibitory concentration (MIC) as they allow the capture of bacterial growth and the development of drug killing rates over time, which allows to compute key pharmacodynamic (PD) parameters. Our study aimed, using a semi-mechanistic mathematical model, to estimate the best pharmacokinetic/pharmacodynamic (PK/PD) indices (ƒAUC/MIC or %ƒT > MIC) for the prediction of clinical efficacy of veterinary FQs in , , and collected from canine pyoderma cases with a focus on the comparison between marbofloxacin and pradofloxacin. Eight TCKs for each bacterial species (4 susceptible and 4 resistant) were analysed in duplicate.

A new Rothamsted long-term field experiment for the twenty-first century: principles and practice.

Unlabelled: Agriculture faces potentially competing societal demands to produce food, fiber and fuel while reducing negative environmental impacts and delivering regulating, supporting and cultural ecosystem services. This necessitates a new generation of long-term agricultural field experiments designed to study the behavior of contrasting cropping systems in terms of multiple outcomes. We document the principles and practices of a new long-term experiment of this type at Rothamsted, established at two contrasting sites in 2017 and 2018, and report initial yield data at the crop and system level.

Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens.

The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2).

Reducing Dietary Acrylamide Exposure from Wheat Products through Crop Management and Imaging.

The nutritional safety of wheat-based food products is compromised by the presence of the processing contaminant acrylamide. Reduction of the key acrylamide precursor, free (soluble, non-protein) asparagine, in wheat grain can be achieved through crop management strategies, but such strategies have not been fully developed. We ran two field trials with 12 soft (biscuit) wheat varieties and different nitrogen, sulfur, potassium, and phosphorus fertilizer combinations.

Quantifying inherent predictability and spatial synchrony in the aphid vector Myzus persicae: field-scale patterns of abundance and regional forecasting error in the UK.

Background: Sugar beet is threatened by virus yellows, a disease complex vectored by aphids that reduces sugar content. We present an analysis of Myzus persicae population dynamics with and without neonicotinoid seed treatment. We use 6 years' yellow water trap and field-collected aphid data and two decades of 12.

Quantitative Pharmacodynamic Characterization of Resistance versus Heteroresistance of Colistin in E. coli Using a Semimechanistic Modeling of Killing Curves.

Heteroresistance corresponds to the presence, in a bacterial isolate, of an initial small subpopulation of bacteria characterized by a significant reduction in their sensitivity to a given antibiotic. Mechanisms of heteroresistance versus resistance are poorly understood. The aim of this study was to explore heteroresistance in -positive and -negative Escherichia coli strains exposed to colistin by use of modeling killing curves with a semimechanistic model.

A heteroskedastic model of Park Grass spring hay yields in response to weather suggests continuing yield decline with climate change in future decades.

UK grasslands perform important environmental and economic functions, but their future productivity under climate change is uncertain. Spring hay yields from 1902 to 2016 at one site (the Park Grass Long Term Experiment) in southern England under four different fertilizer regimes were modelled in response to weather (seasonal temperature and rainfall). The modelling approach applied comprised: (1) a Bayesian model comparison to model parametrically the heteroskedasticity in a gamma likelihood function; (2) a Bayesian varying intercept multiple regression model with an autoregressive lag one process (to incorporate the effect of productivity in the previous year) of the response of hay yield to weather from 1902 to 2016.

Epidemiological Prevalence of Phenotypical Resistances and Mobilised Colistin Resistance in Avian Commensal and Pathogenic from Denmark, France, The Netherlands, and the UK.

Colistin has been used for the treatment of non-invasive gastrointestinal infections caused by avian pathogenic E. coli (APEC). The discovery of mobilised colistin resistance (mcr) in E.

Lipidomics in Understanding Pathophysiology and Pharmacologic Effects in Inflammatory Diseases: Considerations for Drug Development.

The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade.

NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment.

Resolving tumor-associated inflammation in the tumor microenvironment (TME) may promote antitumor effects. Lipoxin A4 (LXA4) is a short-lived endogenous bioactive lipid with potent anti-inflammatory and pro-resolving properties. Here, a biomimetic of LXA4, NAP1051, was shown to have LXA4-like properties and antitumor activity in colorectal cancer xenograft models.

Pharmacokinetics of Colistin in the Gastrointestinal Tract of Poultry Following Dosing via Drinking Water and Its Bactericidal Impact on Enteric .

Colistin, a last-line antibiotic of major importance in veterinary medicine and of critical importance in human medicine, is authorized to treat gastrointestinal (enteric) infections caused by non-invasive in multiple veterinary species including poultry. Its use in veterinary medicine has been implicated in the widespread prevalence of mobilized colistin resistance. The objectives of this study were to determine the intestinal content reached in broiler chickens during 72-h treatment with colistin, to evaluate the associated impact on intestinal density, and to select less susceptible populations.

Reduced free asparagine in wheat grain resulting from a natural deletion of TaASN-B2: investigating and exploiting diversity in the asparagine synthetase gene family to improve wheat quality.

Background: Understanding the determinants of free asparagine concentration in wheat grain is necessary to reduce levels of the processing contaminant acrylamide in baked and toasted wheat products. Although crop management strategies can help reduce asparagine concentrations, breeders have limited options to select for genetic variation underlying this trait. Asparagine synthetase enzymes catalyse a critical step in asparagine biosynthesis in plants and, in wheat, are encoded by five homeologous gene triads that exhibit distinct expression profiles.

Application of the hollow fibre infection model (HFIM) in antimicrobial development: a systematic review and recommendations of reporting.

Objectives: This systematic review focuses on the use of the in vitro hollow fibre infection model (HFIM) for microbial culture. We summarize the direction of the field to date and propose best-practice principles for reporting of the applications.

Methods: Searches in six databases (MEDLINE®, EMBASE®, PubMed®, BIOSIS®, SCOPUS® and Cochrane®) up to January 2020 identified 129 studies meeting our inclusion criteria.