Progress and opportunities through use of genomics in animal production.

The rearing of farmed animals is a vital component of global food production systems, but its impact on the environment, human health, animal welfare, and biodiversity is being increasingly challenged. Developments in genetic and genomic technologies have had a key role in improving the productivity of farmed animals for decades. Advances in genome sequencing, annotation, and editing offer a means not only to continue that trend, but also, when combined with advanced data collection, analytics, cloud computing, appropriate infrastructure, and regulation, to take precision livestock farming (PLF) and conservation to an advanced level. Such an approach could generate substantial additional benefits in terms of reducing use of resources, health treatments, and environmental impact, while also improving animal health and welfare.

NMR-based metabolomics associated with chronic kidney disease in humans and animals: a one health perspective.

Chronic kidney disease (CKD) is a renal dysfunction that can lead to high rates of mortality and morbidity, particularly when coupled with late diagnosis. CKD has become a major health problem due to its challenging detection at early stages when clear symptoms are yet to be presented. Thus, CKD is likely to be identified when the substantive conditions of the disease are manifest. In order to address the development of the disease and provide necessary treatments at the initial stage, the investigation of new biomarkers and metabolites associated with early detection of CKD are needed. Identified metabolites could be used to confirm the presence of the disease, obtain information on its mechanism and facilitate the development of novel pharmaceutical treatments. Such metabolites may be detected from biofluids and tissues using a range of analytical techniques. There are a number of metabolites that have been identified by mass spectrometry at high sensitivities, whilst the detection of metabolites directly from biofluids using NMR could present a more rapid way to expand our understanding of this disease. This review is focused on NMR-based metabolomics associated with CKD in humans and animals.

Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives.

Lysosomal storage disorders (LSDs) are predominantly very rare recessive autosomal neurodegenerative diseases.Sphingolipidoses, a sub-group of LSDs, result from defects in lysosomal enzymes involved in sphingolipid catabolism, and feature disrupted storage systems which trigger complex pathogenic cascades with other organelles collaterally affected. This process leads to cell dysfunction and death, particularly in the central nervous system. One valuable approach to gaining insights into the global impact of lysosomal dysfunction is through metabolomics, which represents a discovery tool for investigating disease-induced modifications in the patterns of large numbers of simultaneously-analysed metabolites, which also features the identification of biomarkers Here, the scope and applications of metabolomics strategies to the investigation of sphingolipidoses is explored in order to facilitate our understanding of the biomolecular basis of these conditions. This review therefore surveys the benefits of applying 'state-of-the-art' metabolomics strategies, both univariate and multivariate, to sphingolipidoses, particularly Niemann-Pick type C disease. Relevant limitations of these techniques are also discussed, along with the latest advances and developments. We conclude that metabolomics strategies are highly valuable, distinctive bioanalytical techniques for probing LSDs, most especially for the detection and validation of potential biomarkers. They also show much promise for monitoring disease progression and the evaluation of therapeutic strategies and targets.

Self-Assembled Anion-Binding Cryptand for the Selective Liquid-Liquid Extraction of Phosphate Anions.

The ligands L1 and L2 form trinuclear self-assembled complexes with Cu2+ (i.e. [(L1 )2 Cu3 ]6+ or [(L2 )2 Cu3 ]6+ ) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions.

Structure-activity modelling of essential oils, their components, and key molecular parameters and descriptors.

Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r2 = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development.

Computational Modeling of a Caged Methyl Cation: Structure, Energetics, and Vibrational Analysis.

DFT calculations for CH3+ within a constrained cage of water molecules permit the controlled manipulation of distances rax and req to "axial" and "equatorial" waters. Equatorial CH···O interactions catalyze methyl transfer (MT) between axial waters. Variation in rax has a greater effect on CH bond lengths and stretching force constants in the symmetric SN2-like transition structures than variation in req. In-plane bending frequencies are insensitive to these variations in cage dimensions, but axial interactions loosen the out-of-plane bending mode (OP) whereas equatorial interactions stiffen it. Frequencies for rotational and translational motions of CH3+ within the cage are influenced by rax and req. In particular, translation of CH3+ in the axial direction is always coupled to cage motion. With longer rax, CH3+ translation is coupled with asymmetric CO bond stretching, but with shorter rax, it is also coupled with OP (equivalent to the umbrella mode of trigonal bipyramidal O···CH3+···O); the magnitude of the imaginary MT frequency increases steeply as rax diminishes. This coupling between CH3+ and its cage is removed by eliminating the rows and columns associated with cage atoms from the full Hessian to obtain a reduced Hessian for CH3+ alone. Within a certain range of cage dimensions, the reduced Hessian yields a real frequency for MT. The importance of using a Hessian large enough to describe the reaction coordinate mode correctly is emphasized for modeling chemical reactions and particularly for kinetic isotope effects in enzymic MT.

A computational study of the influence of methyl substituents on competitive ring closure to α- and ß-lactones.

Ring-closure of substituted 2-chlorosuccinates to α- or ß-lactones has been studied by means of MP2/6-311+G(d,p)//MP2/6-31+G(d) calculations in water treated as a polarised continuum (PCM) and in vacuum. Optimised geometries have been obtained for 2-chlorosuccinate and its 2-methyl, 3,3-dimethyl, and 2,3,3-trimethyl derivatives, along with the transition structures and products for intramolecular nucleophilic displacement leading to the 3- or 4-membered rings. Relative enthalpies and Gibbs free energies of activation and reaction are presented, along with key geometrical parameters, and changes in electrostatic-potential-derived atomic charges. The difference in free-energy barriers for α- and ß-lactone formation from the 2-methyl substrate at 298 K is less than 1 kJ mol-1. Primary 14C kinetic isotope effects calculated for substitution at C2 are significantly smaller for α-lactone formation than for ß, suggesting a possible way to distinguish between the competing pathways of reaction. The B3LYP method without dispersion corrections predicts the wrong relative stability order for methyl-substituted succinate dianions in PCM water.

Influence of Equatorial CH⋠⋠⋠O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer.

DFT calculations for methyl cation complexed within a constrained cage of water molecules permit the controlled manipulation of the "axial" donor/acceptor distance and the "equatorial" distance to hydrogen-bond acceptors. The kinetic isotope effect k(CH3)/k(CT3) for methyl transfer within a cage with a short axial distance becomes less inverse for shorter equatorial C⋅⋅⋅O distances: a decrease of 0.5 Šresults in a 3 % increase at 298 K. Kinetic isotope effects in AdoMet-dependent methyltransferases may be m∧odulated by CH⋅⋅⋅O hydrogen bonding, and factors other than axial compression may contribute, at least partially, to recently reported isotope-effect variations for catechol-O-methyltransferase and its mutant structures.

Genomic characterisation of bioaerosols within livestock facilities: A systematic review.

Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the past decade, bioaerosol studies have increasingly utilised high throughput sequencing (HTS) to achieve superior throughput, taxonomic resolution, and the detection of unculturable organisms. However, the prevailing focus on amplicon sequencing has limited the identification of viruses and microbial taxa at the species-level. Herein, a literature search was conducted to identify methods capable of overcoming the aforementioned limitations. Screening 1531 international publications resulted in 29 eligible for review. Metagenomics capable of providing rich insights were identified in only three instances. Notably, long-read sequencing was not utilised for metagenomics. This review also identified that sample collection methods lack a uniform approach, highlighted by the differences in sampling equipment, flow rates and durations. Further heterogeneity was introduced by the unique sampling conditions, which makes it challenging to ground new findings within the established literature. For instance, winter was associated with increased microbial abundance and antimicrobial resistance, yet less alpha diversity. Researchers implementing metagenomics into the livestock environment should consider season, the microclimate, and livestock growth stage as influential upon their findings. Considering the increasing accessibility of long-read sequencing, future research should explore its viability within a novel uniform testing protocol for bioaerosol emissions.

Microarray molecular mapping of horses with severe asthma.

BACKGROUND: Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. ANIMALS: Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). METHODS: This intentional cross-sectional study investigated the sensitization profiles of SA-affected and healthy horses via serological antigen microarray profiling. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non-affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. RESULTS: PLS-DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions.

Organisational capabilities, outcomes, and benefits of trigger finger release surgery in primary care: a service evaluation study.

BACKGROUND: Trigger finger is a common hand condition in which a finger is unable to fully extend owing to a thickening of the tendon and its sheath, causing the finger to lock in a bent position. AIM: To assess the viability of carrying out trigger finger surgeries in NHS primary care in terms of clinician and patient acceptance, experience, and outcomes; and operational requirements of this service for wider application. DESIGN & SETTING: A pilot study for a new service in primary care in Leicestershire, UK. METHOD: A total of 214 trigger finger release surgery procedures were carried out between 22 August 2019 and 25 October 2022 by a single hand surgeon in a single primary care surgery. Data were analysed using information from SystmOne, which is a patient database linked with the NHS. RESULTS: Thirty-two cases out of 214 (15.0%) experienced a wait time of <10 days from the GP referral to the first outpatient appointment (OPA). Out of 214 procedures, there were 26 (12.1%) postoperative complications that required follow-up action. Of the total number of cases where postoperative complications were identified, 13 cases required further follow-up action, while the remaining 13 did not have any identifiable further follow-up action and were regarded as closed cases thereafter. CONCLUSION: Trigger finger release surgery in primary care offers an opportunity to reduce pressures on secondary care orthopaedic referrals, as well as offering patients faster and effective surgical treatment while utilising fewer NHS resources.

Infrared and Raman Diagnostic Modeling of Phosphate Adsorption on Ceria Nanoparticles.

Cerium dioxide (CeO2; ceria) nanoparticles (CeNPs) are promising nanozymes that show a variety of biological activity. Effective nanozymes need to retain their activity in the face of surface speciation in biological environments, and characterizing surface speciation is therefore critical to understanding and controlling the therapeutic capabilities of CeNPs. In particular, adsorbed phosphates can impact the enzymatic activity exploited to convert phosphate prodrugs into therapeutics in vivo and also define the early stages of the phosphate-scavenging processes that lead to the transformation of active CeO2 into inactive CePO4. In this work, we utilize ab initio lattice-dynamics calculations to study the interaction of phosphates with the three major surfaces of ceria and to predict the infrared (IR) and Raman spectral signatures of adsorbed phosphate species. We find that phosphates adsorb strongly to CeO2 surfaces in a range of stable binding configurations, of which 5-fold coordinated P species in a trigonal bipyramidal coordination may represent a stable intermediate in the early stages of phosphate scavenging. We find that the phosphate species show characteristic spectral fingerprints between 500 and 1500 cm-1, whereas the bare CeO2 surfaces show no active modes above 600 cm-1, and the 5-fold coordinated P species in particular show potential diagnostic P-O stretching modes between 650 and 700 cm-1 in both IR and Raman spectra. This comprehensive exploration of different binding modes for phosphates on CeO2 and the set of reference spectra provides an important step toward the experimental characterization of phosphate speciation and, ultimately, control of its impact on the performance of ceria nanozymes.

Computational Investigation of Ligand Binding of Flavonoids in Cytochrome P450 Receptors.

AIM: The cytochrome P450 enzymes play a significant role in regulating cellular and physiological processes by activating endogenous compounds. They also play an essential role in the detoxification process of xenobiotics. Flavonoids belong to a class of polyphenols found in food, such as vegetables, red wine, beer, and fruits, which modulate biological functions in the body. METHODS: The inhibition of CYP1A1 and CYP1B1 using nutritional sources has been reported as a strategy for cancer prevention. This study investigated the interactions of selected flavonoids binding to the cytochrome P450 enzymes (CYP1A1 and CYP1B1) and their ADMET properties in silico. From docking studies, our findings showed flavonoids, isorhamnetin and pedalitin, to have the strongest binding energies in the crystal structures 6DWM and 6IQ5. RESULTS: The amino acid residues Asp 313 and Phe 224 in 6DWM interacted with all the ligands investigated, and Ala 330 in 6IQ5 interacted with all the ligands examined. The ligands did not violate any drug-likeness parameters. CONCLUSION: These data suggest roles for isorhamnetin and pedalitin as potential precursors for natural product- derived therapies.

Minireview: Applications of NMR-based metabolomics for the detection and characterisation of toxoplasmosis in felids.

Toxoplasmosis is an infection caused by the intercellular protozoan parasite Toxoplasma gondii. The parasite has the three-stage life cycle: oocysts, tachyzoites, and bradyzoites. Felids are the only known hosts for the sexual reproduction of T. gondii and, therefore, play a crucial role in the transmission of toxoplasmosis. A single cat could spread the parasite to many hosts. Due to the intercellular nature of the parasite, T. gondii strongly depends on a host's metabolism in order to leverage carbon and nutrient sources. Therefore, the parasite could be detected in body fluids via observation and analysis of metabolic alterations. A range of analytical techniques such as nuclear magnetic resonance (NMR), mass spectrometry coupled with liquid chromatography, and Raman spectroscopy could be applied for the analysis of body fluids of infected animals. However, NMR consists of highly specific analytical techniques due to high reproducibility, availability of a variety of databases, and the ability to obtain the structures of unknown compounds. We present the current extent of NMR-based metabolomics on felid toxoplasmosis and suggest future considerations.

16 Years of breed management brings substantial improvement in population genetics of the endangered Cleveland Bay Horse.

The consequences of poor breed management and inbreeding can range from gradual declines in individual productivity to more serious fertility and mortality concerns. However, many small and closed groups, as well as larger unmanaged populations, are plagued by genetic regression, often due to a dearth in breeding support tools which are accessible and easy to use in supporting decision-making. To address this, we have developed a population management tool (BCAS, Breed Conservation and Management System) based on individual relatedness assessed using pedigree-based kinship, which offers breeding recommendations for such populations. Moreover, we demonstrate the success of this tool in 16 years of employment in a closed equine population native to the UK, most notably, the rate of inbreeding reducing from more than 3% per generation, to less than 0.5%, or that attributed to genetic drift, as assessed over the last 16 years of implementation. Furthermore, with adherence to this program, the long-term impact of poor management has been reversed and the genetic resource within the breed has grown from an effective population size of 20 in 1994 to more than 140 in 2020. The development and availability of our BCAS for breed management and selection establish a new paradigm for the successful maintenance of genetic resources in animal populations.

Recent applications of electrical, centrifugal, and pressurised emerging technologies for fibrous structure engineering in drug delivery, regenerative medicine and theranostics.

Advancements in technology and material development in recent years has led to significant breakthroughs in the remit of fiber engineering. Conventional methods such as wet spinning, melt spinning, phase separation and template synthesis have been reported to develop fibrous structures for an array of applications. However, these methods have limitations with respect to processing conditions (e.g. high processing temperatures, shear stresses) and production (e.g. non-continuous fibers). The materials that can be processed using these methods are also limited, deterring their use in practical applications. Producing fibrous structures on a nanometer scale, in sync with the advancements in nanotechnology is another challenge met by these conventional methods. In this review we aim to present a brief overview of conventional methods of fiber fabrication and focus on the emerging fiber engineering techniques namely electrospinning, centrifugal spinning and pressurised gyration. This review will discuss the fundamental principles and factors governing each fabrication method and converge on the applications of the resulting spun fibers; specifically, in the drug delivery remit and in regenerative medicine.

Preliminary demonstration of benchtop NMR metabolic profiling of feline urine: chronic kidney disease as a case study.

OBJECTIVE: The use of benchtop metabolic profiling technology based on nuclear magnetic resonance (NMR) was evaluated in a small cohort of cats with a view to applying this as a viable and rapid metabolic tool to support clinical decision making. RESULTS: Urinary metabolites were analysed from four subjects consisting of two healthy controls and two chronic kidney disease (CKD) IRIS stage 2 cases. The study identified 15 metabolites in cats with CKD that were different from the controls. Among them were acetate, creatinine, citrate, taurine, glycine, serine and threonine. Benchtop NMR technology is capable of distinguishing between chronic kidney disease case and control samples in a pilot feline cohort based on metabolic profile. We offer perspectives on the further development of this pilot work and the potential of the technology, when combined with sample databases and computational intelligence techniques to offer a clinical decision support tool not only for cases of renal disease but other metabolic conditions in the future.

Potential Adverse Public Health Effects Afforded by the Ingestion of Dietary Lipid Oxidation Product Toxins: Significance of Fried Food Sources.

Exposure of polyunsaturated fatty acid (PUFA)-rich culinary oils (COs) to high temperature frying practices generates high concentrations of cytotoxic and genotoxic lipid oxidation products (LOPs) via oxygen-fueled, recycling peroxidative bursts. These toxins, including aldehydes and epoxy-fatty acids, readily penetrate into fried foods and hence are available for human consumption; therefore, they may pose substantial health hazards. Although previous reports have claimed health benefits offered by the use of PUFA-laden COs for frying purposes, these may be erroneous in view of their failure to consider the negating adverse public health threats presented by food-transferable LOPs therein. When absorbed from the gastrointestinal (GI) system into the systemic circulation, such LOPs may significantly contribute to enhanced risks of chronic non-communicable diseases (NCDs), e.g. cancer, along with cardiovascular and neurological diseases. Herein, we provide a comprehensive rationale relating to the public health threats posed by the dietary ingestion of LOPs in fried foods. We begin with an introduction to sequential lipid peroxidation processes, describing the noxious effects of LOP toxins generated therefrom. We continue to discuss GI system interactions, the metabolism and biotransformation of primary lipid hydroperoxide LOPs and their secondary products, and the toxicological properties of these agents, prior to providing a narrative on chemically-reactive, secondary aldehydic LOPs available for human ingestion. In view of a range of previous studies focused on their deleterious health effects in animal and cellular model systems, some emphasis is placed on the physiological fate of the more prevalent and toxic α,ß-unsaturated aldehydes. We conclude with a description of targeted nutritional and interventional strategies, whilst highlighting the urgent and unmet clinical need for nutritional and epidemiological trials probing relationships between the incidence of NCDs, and the frequency and estimated quantities of dietary LOP intake.

Genetic analysis of the endangered Cleveland Bay horse: A century of breeding characterised by pedigree and microsatellite data.

The Cleveland Bay horse is one of the oldest equines in the United Kingdom, with pedigree data going back almost 300 years. The studbook is essentially closed and because of this, there are concerns about loss of genetic variation across generations. The breed is one of five equine breeds listed as "critical" (<300 registered adult breeding females) by the UK Rare Breeds Survival Trust in their annual Watchlist. Due to their critically endangered status, the current breadth of their genetic diversity is of concern, and assessment of this can lead to improved breed management strategies. Herein, both genealogical and molecular methods are combined in order to assess founder representation, lineage, and allelic diversity. Data from 15 microsatellite loci from a reference population of 402 individuals determined a loss of 91% and 48% of stallion and dam lines, respectively. Only 3 ancestors determine 50% of the genome in the living population, with 70% of maternal lineage being derived from 3 founder females, and all paternal lineages traced back to a single founder stallion. Methods and theory are described in detail in order to demonstrate the scope of this analysis for wider conservation strategies. We quantitatively demonstrate the critical nature of the genetic resources within the breed and offer a perspective on implementing this data in considered breed management strategies.