Study of urgent visits to commercial rabbit farms in Spain and Portugal during 1997-2007

[EN] This is a report on work carried out on 4307 visits to 868 commercial farms with domestic rabbits in Spain and Portugal from January 1997 to December 2007. Of the total visits, 2237 (52%) were emergencies on 660 farms. The median size of the farms ranged between 450 does in 1997 and 750 in 2007. This retrospective study measures the clinical disease occurrence using the Monthly Risk of urgent visits (MR), i.e. the percentage of visits made as a result of each clinical disease in comparison with the total number of urgent visits made each month. The main reasons for the emergencies were mucoid enteropathy (similar to Epizootic Rabbit Enteropathy), with a MR: 25.0%, enteritis-diarrhoea (24.1%), myxomatosis, (11.1%), reproductive troubles (8.6%), respiratory diseases (7.2%) and staphylococcosis (4.2%). Fifty-four percent of the urgent visits were due to diseases of the digestive system. Mucoid enteropathy was still one of the main diseases faced by the commercial rabbit industry during the study period. No significant yearly or monthly variations were observed in the analysis of the MR. A seasonal effect was only found in respiratory diseases during the summer (MR: 11.06±0.01) and myxomatosis in autumn (MR: 14.60±0.02), in comparison with spring (MR: 7.44±0.02). It is therefore concluded that farms should be permanently protected as they might be affected by any of these diseases at any time during the year.Rosell, J.; Fuente, LDL.; Badiola, J.; Fernández De Luco, D.; Casal, J.; Saco, M. (2009). Study of urgent visits to commercial rabbit farms in Spain and Portugal during 1997-2007. World Rabbit Science. 17(3):127-136. doi:10.4995/wrs.2009.65212713617

Assessment of hydrocarbon pollution in NW Iberian Peninsula using bioaccumulation and molecular biomarkers in Mytilus galloprovincialis

Society of Environmental Toxicology and Chemistry - SETAC Europe 15th Annual Meeting, Lille, France, May 2005.Polycyclic aromatic hydrocarbons (PAH´s) are ubiquitous contaminants in marine environment as a result of uncontrolled spills, river transport, surface runoff and atmospheric deposition. A significant amount of industrial activity including shipping and oil refining is located along the NW Iberian Peninsula coast. The use of exposure biomarkers holds out promise due to the incipient state of the cost-effective methodologies for diagnosis and monitoring of oil pollution. This work presents the preliminary results concerning the identification of a set of biomarkers for an early warning detection of PAH toxicity. The bivalve Mytillus galloprovincialis was selected due to its ubiquitous distribution along coastline, being used as sentinels in pollution monitoring. This species has also an important value. Four locations in the vicinity of industrial wastewater discharges along the NW Iberian coast were selected and compared with a nearby (reference) site for (i) measurements of PAH body burdens and (ii) levels of enzyme activity: catalase (CAT), superoxide-dismutase (SOD), glutathione peroxidase (GPx), gluthathione S-transferase (GST) and Na+/K+ATPase (ATPase). The results will be discussed on the basis of their potential in providing additional evidence for discriminate between well known polluted and unpolluted sites

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C-reactive protein and hair cortisol sampled at the time of slaughter

Background: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). Results: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having ‘moderate’ accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). Conclusion: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn

Soil-derived Nature’s Contributions to People and their contribution to the UN Sustainable Development Goals

Acknowledgments The input of PS contributes to Soils-R-GRREAT (NE/P019455/1) and the input of PS and SK contributes to the European Union's Horizon 2020 Research and Innovation Programme through project CIRCASA (grant agreement no. 774378). PR acknowledges funding from UK Greenhouse Gas Removal Programme (NE/P01982X/2). GB De Deyn acknowledges FoodShot Global for its support. TKA acknowledges the support of “Towards Integrated Nitrogen Management System (INMS) funded by the Global Environment Facility (GEF), executed through the UK’s Natural Environment Research Council (NERC). The input of DG was supported by the New Zealand Ministry of Business, Innovation and Employment (MBIE) strategic science investment fund (SSIF). PMS acknowledges support from the Australian Research Council (Project FT140100610). PM’s work on ecosystem services is supported by a National Science Foundation grant #1853759, “Understanding the Use of Ecosystem Services Concepts in Environmental Policy”. LGC is funded by National Council for Scientific and Technological Development (CNPq, Brazil – grants 421668/2018-0 and 305157/2018-3) and by Lisboa2020 FCT/EU (project 028360). BS acknowledges support from the Lancaster Environment Centre Project.Peer reviewedPostprin

Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves

The effects of different amino acid (AA) supplementations of milk protein-based milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied. Animals were divided into 4 groups: Ctrl) Control group fed with milk protein-based milk replacer without supplementation; GP) supplementation with 0.1% glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2% tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61% threonine. For statistical analysis, t-test was used to compare AA-supplemented animals to the Ctrl group. At week 7, body weight and average daily gain (ADG) were measured and blood samples and skeletal muscle biopsies were taken. Blood biochemistry analytes related to energy metabolism were determined and it was shown that MKT group had higher serum creatinine and higher plasma concentration of three supplemented AAs as well as arginine compared with the Ctrl group. GP group had similar glycine/proline plasma concentration compared with the other groups while in FY group only plasma phenylalanine concentration was higher compared with Control. Although the AA supplementations in the GP and FY groups did not affect average daily gain and metabolic health profile from serum, the metabolome analysis from skeletal muscle biopsy revealed several differences between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic adaptation especially in GP and FY groupsinfo:eu-repo/semantics/publishedVersio

Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

Background: Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods: We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT) when its association with a particular metabolic trait achieved a nominal P value < 0.01. Results: A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions: These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues