| 1. |
- Wiszmeg, Andréa, et al.
(författare)
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Transforming trash to treasure Cultural ambiguity in foetal cell research
- 2021
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Ingår i: Philosophy Ethics and Humanities in Medicine. - : Springer Science and Business Media LLC. - 1747-5341. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. Methods This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson's disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas's concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva's concept of the abjective to explain and make sense of the findings. Results The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. Conclusions The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.
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| 2. |
- Hajkazemian, Melika, 1988-
(författare)
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Decoding the language of transmission among vector-pathogen-host
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vector-borne diseases account for over 17 percent of all infectious diseases and lead to more than 700,000 mortalities annually. Importantly, there is a complex interaction between infectious organisms and their host. Vectors spread pathogens, which have a significant negative health effect on humans and animals and therefore detrimental economic and environmental impacts. Only 2% of the more than 3,600 mosquito species are blood feeders, primarily; the Anopheles, Culex, and Aedes which spread the Malaria parasite, Zika, Chikungunya, West Nile, and Dengue viruses. Therefore, understanding the complex chemical signaling and the molecular mechanisms that mediate pathogen and vector interaction, and allow the pathogen to survive and spread, are the subjects of this thesis.In project I, we determined the production and release of Anopheles male aggregation Volatile Organic Compounds (VOCs) that initiate swarming, and enhance mating success. In addition, we compared the RNA-sequencing libraries of swarming to flag for chemosensory and circadian genes. The goal was to identify the molecular mechanisms of swarming and metabolite roles in mating success.In project II, we evaluated the phagostimulant effects of (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) on an artificial feeding system for some important vectors (Anopheles coluzzii, An. arabiensis, An. gambiae s.s., Culex pipiens/Culex torrentium, and Aedes aegypti). We showed that our toxic plant-based solution can kill the five lethal vectors.In project III, we studied the alteration of An. gambiae behavior by the Plasmodium falciparum at infected (oocyst-carrying, 7 days post-infection) and infective (sporozoite-carrying, 14 days post-infection) stages. To discover whether antennal chemosensory genes expression changes at different stages of infection, we performed RNA-seq and examined the candidate olfactory genes’ abundance to provide a possible molecular mechanism for manipulating the parasite-carrying mosquitoes' behavior.Finally, in project IV, we presented the results of RNA-seq analysis that revealed the network connection between developmental genes and the physiological plasticity in male mosquitoes of An. funestus. We identified the transcripts that associated with the male An. funestus sexual maturation and mating success.In summary, this thesis focuses on understanding how vector-pathogen interaction manipulates the vector’s transcriptome, physiology, and behavior to enhance transmission success and thereby identify novel targets for vector-borne disease control.
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| 3. |
- Karlsson, Therese, 1979, et al.
(författare)
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Identification of Single and Combined Serum Metabolites Associated with Food Intake
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of dietary intake is challenging. Traditional methods suffer from both random and systematic errors; thus objective measures are important complements in monitoring dietary exposure. The study presented here aims to identify serum metabolites associated with reported food intake and to explore whether combinations of metabolites may improve predictive models. Fasting blood samples and a 4-day weighed food diary were collected from healthy Swedish subjects (n = 119) self-defined as having habitual vegan, vegetarian, vegetarian + fish, or omnivore diets. Serum was analyzed for metabolites by 1H-nuclear magnetic resonance spectroscopy. Associations between single and combined metabolites and 39 foods and food groups were explored. Area under the curve (AUC) was calculated for prediction models. In total, 24 foods or food groups associated with serum metabolites using the criteria of rho > 0.2, p < 0.01 and AUC ≥ 0.7 were identified. For the consumption of soybeans, citrus fruits and marmalade, nuts and almonds, green tea, red meat, poultry, total fish and shellfish, dairy, fermented dairy, cheese, eggs, and beer the final models included two or more metabolites. Our results indicate that a combination of metabolites improve the possibilities to use metabolites to identify several foods included in the current diet. Combined metabolite models should be confirmed in dose–response intervention studies.
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| 4. |
- Akula, Srinivas, et al.
(författare)
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Quantitative Transcriptome Analysis of Purified Equine Mast Cells Identifies a Dominant Mucosal Mast Cell Population with Possible Inflammatory Functions in Airways of Asthmatic Horses
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:22
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a chronic inflammatory airway disease and a serious health problem in horses as well as in humans. In humans and mice, mast cells (MCs) are known to be directly involved in asthma pathology and subtypes of MCs accumulate in different lung and airway compartments. The role and phenotype of MCs in equine asthma has not been well documented, although an accumulation of MCs in bronchoalveolar lavage fluid (BALF) is frequently seen. To characterize the phenotype of airway MCs in equine asthma we here developed a protocol, based on MACS Tyto sorting, resulting in the isolation of 92.9% pure MCs from horse BALF. We then used quantitative transcriptome analyses to determine the gene expression profile of the purified MCs compared with total BALF cells. We found that the MCs exhibited a protease profile typical for the classical mucosal MC subtype, as demonstrated by the expression of tryptase (TPSB2) alone, with no expression of chymase (CMA1) or carboxypeptidase A3 (CPA3). Moreover, the expression of genes involved in antigen presentation and complement activation strongly implicates an inflammatory role for these MCs. This study provides a first insight into the phenotype of equine MCs in BALF and their potential role in the airways of asthmatic horses.
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| 5. |
- Haubro Andersen, Pia, et al.
(författare)
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Towards Machine Recognition of Facial Expressions of Pain in Horses
- 2021
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Ingår i: Animals. - : MDPI. - 2076-2615. ; 11:6
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Facial activity can convey valid information about the experience of pain in a horse. However, scoring of pain in horses based on facial activity is still in its infancy and accurate scoring can only be performed by trained assessors. Pain in humans can now be recognized reliably from video footage of faces, using computer vision and machine learning. We examine the hurdles in applying these technologies to horses and suggest two general approaches to automatic horse pain recognition. The first approach involves automatically detecting objectively defined facial expression aspects that do not involve any human judgment of what the expression "means". Automated classification of pain expressions can then be done according to a rule-based system since the facial expression aspects are defined with this information in mind. The other involves training very flexible machine learning methods with raw videos of horses with known true pain status. The upside of this approach is that the system has access to all the information in the video without engineered intermediate methods that have filtered out most of the variation. However, a large challenge is that large datasets with reliable pain annotation are required. We have obtained promising results from both approaches. Automated recognition of human facial expressions of pain and emotions is to a certain degree a solved problem, using approaches based on computer vision and machine learning. However, the application of such methods to horses has proven difficult. Major barriers are the lack of sufficiently large, annotated databases for horses and difficulties in obtaining correct classifications of pain because horses are non-verbal. This review describes our work to overcome these barriers, using two different approaches. One involves the use of a manual, but relatively objective, classification system for facial activity (Facial Action Coding System), where data are analyzed for pain expressions after coding using machine learning principles. We have devised tools that can aid manual labeling by identifying the faces and facial keypoints of horses. This approach provides promising results in the automated recognition of facial action units from images. The second approach, recurrent neural network end-to-end learning, requires less extraction of features and representations from the video but instead depends on large volumes of video data with ground truth. Our preliminary results suggest clearly that dynamics are important for pain recognition and show that combinations of recurrent neural networks can classify experimental pain in a small number of horses better than human raters.
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| 6. |
- Sharif, Hanan, et al.
(författare)
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A monoclonal antibody-based sandwich ELISA for measuring canine Thymidine kinase 1 protein and its role as biomarker in canine lymphoma
- 2023
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Dogs play an important role in society, which increased during the covid epidemics. This has led to a much higher workload for the veterinarians. Therefore, there is a need for efficient diagnostic tools to identify risk of malignant diseases. Here the development of a new test that can solve some of these problems is presented. It is based on serum Thymidine Kinase 1 (TK1), which is a biomarker for cell proliferation and cell lysis.Methods: Anti-TK1 monoclonal antibodies were produced against two different epitopes, the active site of the TK1 protein and the C-terminal region of canine TK1. The antibodies were developed with hybridoma technology and validated using dot blot, Quartz Crystal Microbalance (QCM) technology, western blots, immunoprecipitation (IP), and enzyme-linked immunosorbent assay (ELISA). Clinical evaluation of Canine TK1 ELISA was done by using sera from 131 healthy dogs and 93 dogs with lymphoma. The two selected Anti-TK1 monoclonal antibodies have Kd values in the range of 10(-9) M and further analysis with dot and western blots confirmed the high affinity binding of these antibodies. A sandwich Canine TK1 ELISA was developed using the anti-TK1 antibodies, and TK1 concentrations in serum samples were determined using dog recombinant TK1 as a standard.Results: Serum TK1 protein levels were significantly higher in dogs with lymphoma compared to those in healthy dogs (p < 0.0001). Receiver operating curve analysis showed that the canine TK1-ELISA obtain a sensitivity of 0.80, at a specificity of 0.95. Moreover, the Canine TK1 ELISA has a positive predictive value (PPV) of 97%, and the negative predictive value (NPV) of 83%, reflecting the proportion of test results that are truly positive and negative. Furthermore, Canine TK1 ELISA had significantly higher capacity to differentiate dogs with T-cell lymphoma from those with B-cell lymphoma compared to earlier used TK1 activity assays.Discussion: These results demonstrate that the Canine TK1 ELISA can serve as an efficient tool in the diagnosis and management of dogs with lymphomas.
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| 7. |
- Sharma, Garima, et al.
(författare)
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A qualitative study on antibiotic use and animal health management in smallholder dairy farms of four regions of India
- 2020
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Ingår i: Infection Ecology & Epidemiology. - : Taylor & Francis. - 2000-8686. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAntimicrobial resistance (AMR) is a major global public health issue. In India, access to medicines is poorly regulated and therefore antibiotics in dairy cattle are commonly used by farmers without consulting with veterinarians. This study was conducted to understand practices and knowledge related to antibiotic use and AMR among dairy farmers and veterinary professionals in selected urban and peri-urban areas of India.MethodsA total of 28 focus group discussions with farmers and 53 interviews with veterinary professionals were carried out.ResultsMastitiswas identified as the main animal health challenge. Antibiotic consultation behavior of farmers depended on the availability of veterinarians. Except in Bangalore, farmers were found to often treat animals on their own. They were found unaware of the concept of AMR, but knew the importance of vaccination. Veterinarians included in the study had a good understanding of antibiotics, AMR, and zoonotic diseases.ConclusionThe knowledge level and practices observed in the study related to the use/abuse of antibiotics can potentially increase the risk of development of AMR and its transfer in the community. Our findings can help support AMR – mitigation efforts in the country, including the design of better policies on antibiotic use in dairy.
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| 8. |
- Malaluang, Pongpreecha, et al.
(författare)
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Antimicrobial Resistance in Equine Reproduction
- 2021
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Ingår i: Animals. - : MDPI. - 2076-2615. ; 11:11
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Forskningsöversikt (refereegranskat)abstract
- Simple SummaryBacteria can develop resistance to antibiotics, resulting in the appearance of infections that are difficult or impossible to treat. This ability enables bacteria to survive in hostile environments and can result from exposure to even small amounts of antibiotic substances. Bacteria are present in the reproductive tract of the horse; they can develop resistance to antibiotics, because the animal has been treated for an infection, or due to insemination with a semen dose that contains antibiotics. Bacteria colonize the membrane lining the male reproductive tract and are transferred to the semen during collection. They can cause sperm quality to deteriorate during storage or may cause an infection in the mare. Therefore, antibiotics are added to the semen dose, according to legislation. However, these antibiotics may contribute to the development of resistance. Current recommendations are that antibiotics should only be used to treat bacterial infections and where the sensitivity of the bacterium to the antibiotic has first been established. Therefore, adding antibiotics to semen extenders does not fit these recommendations. In this review, we examine the effects of bacteria in semen and in the inseminated mare, and possible alternatives to their use.Bacteria develop resistance to antibiotics following low-level "background " exposure to antimicrobial agents as well as from exposure at therapeutic levels during treatment for bacterial infections. In this review, we look specifically at antimicrobial resistance (AMR) in the equine reproductive tract and its possible origin, focusing particularly on antibiotics in semen extenders used in preparing semen doses for artificial insemination. Our review of the literature indicated that AMR in the equine uterus and vagina were reported worldwide in the last 20 years, in locations as diverse as Europe, India, and the United States. Bacteria colonizing the mucosa of the reproductive tract are transferred to semen during collection; further contamination of the semen may occur during processing, despite strict attention to hygiene at critical control points. These bacteria compete with spermatozoa for nutrients in the semen extender, producing metabolic byproducts and toxins that have a detrimental effect on sperm quality. Potential pathogens such as Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa may occasionally cause fertility issues in inseminated mares. Antibiotics are added during semen processing, according to legislation, to impede the growth of these microorganisms but may have a detrimental effect on sperm quality, depending on the antimicrobial agent and concentration used. However, this addition of antibiotics is counter to current recommendations on the prudent use of antibiotics, which recommend that antibiotics should be used only for therapeutic purposes and after establishing bacterial sensitivity. There is some evidence of resistance among bacteria found in semen samples. Potential alternatives to the addition of antibiotics are considered, especially physical removal separation of spermatozoa from bacteria. Suggestions for further research with colloid centrifugation are provided.
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| 9. |
- Dube, Faruk, et al.
(författare)
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Transcriptomics of ivermectin response in Caenorhabditis elegans : Integrating abamectin quantitative trait loci and comparison to the Ivermectin-exposed DA1316 strain
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10(-7) and 10(-8) M) for 4 hours at 20 degrees C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL.
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| 10. |
- Sharma, Garima, et al.
(författare)
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Antibiotic use, knowledge, and practices of milk vendors in India's informal dairy value chain
- 2022
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Ingår i: Frontiers in Sustainable Food Systems. - : Frontiers Media S.A.. - 2571-581X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Milk vendors play an important role in India's dairy value chain; however, their food safety practices are poorly understood. From the standpoint of milk safety, vendor behavior is significant because it has the potential to affect both consumer and producer behavior. This study investigates vendors' hygienic knowledge and practices toward milk safety, and antimicrobial resistance (AMR)Methods: A cross-sectional study was conducted in the states of Assam and Haryana (India). In selected villages, all the milk vendors identified at the time of the visit were interviewed. A questionnaire was used to assess the knowledge and practices on antibiotics, milk safety, and hygiene. The milk samples were tested for the presence of antibiotic-resistant bacteria using antibiotic susceptibility testing.Results: A total of 2444 milk vendors were interviewed during the survey. Out of these 156 (59.8%) of the vendors traded in raw milk while 40.2% traded in pasteurizes milk. Vendors were categorized depending on whom they supplied milk. Five categories were identified: (a) those who sold at grocery shops; (b) those who sold on the roadside; (c) those who sold from door to door; (d) those who sold to sweet makers/tea stalls; (e) those who sold from own home/other entity. The level of training among vendors on milk hygiene was non-existent and the knowledge related to antibiotics was low. Most of them (86.07%) agreed that boiled milk is always safer than raw milk but almost half (48.77%) of them admitted that sometimes they drink milk without boiling it. Most vendors believed that they could identify whether milk is safe or not for consumption just by its appearance and smell. Out of 124 milk samples collected from surveyed milk vendors and tested for the presence of antibiotic-resistant bacteria, 80 (64.52%) tested positive.Conclusion: This study highlights the low levels of knowledge regarding food safety among milk vendors. It shows the predominance of informal milk businesses in the surveyed states and the prevalence of AMR bacteria in milk traded by them. Training may be a beneficial strategy for addressing the issue.
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| 11. |
- Rashid, Maheen, et al.
(författare)
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Equine Pain Behavior Classification via Self-Supervised Disentangled Pose Representation
- 2022
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Ingår i: 2022 IEEE WINTER CONFERENCE ON APPLICATIONS OF COMPUTER VISION (WACV 2022). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 152-162
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Konferensbidrag (refereegranskat)abstract
- Timely detection of horse pain is important for equine welfare. Horses express pain through their facial and body behavior, but may hide signs of pain from unfamiliar human observers. In addition, collecting visual data with detailed annotation of horse behavior and pain state is both cumbersome and not scalable. Consequently, a pragmatic equine pain classification system would use video of the un-observed horse and weak labels. This paper proposes such a method for equine pain classification by using multi-view surveillance video footage of unobserved horses with induced orthopaedic pain, with temporally sparse video level pain labels. To ensure that pain is learned from horse body language alone, we first train a self-supervised generative model to disentangle horse pose from its appearance and background before using the disentangled horse pose latent representation for pain classification. To make best use of the pain labels, we develop a novel loss that formulates pain classification as a multi-instance learning problem. Our method achieves pain classification accuracy better than human expert performance with 60% accuracy. The learned latent horse pose representation is shown to be viewpoint covariant, and disentangled from horse appearance. Qualitative analysis of pain classified segments shows correspondence between the pain symptoms identified by our model, and equine pain scales used in veterinary practice.
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| 12. |
- Stingo Hirmas, Diego Vittorio, et al.
(författare)
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Proportional Cerebellum Size Predicts Fear Habituation in Chickens
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The cerebellum has a highly conserved neural structure across species but varies widely in size. The wide variation in cerebellar size (both absolute and in proportion to the rest of the brain) among species and populations suggests that functional specialization is linked to its size. There is increasing recognition that the cerebellum contributes to cognitive processing and emotional control in addition to its role in motor coordination. However, to what extent cerebellum size reflects variation in these behavioral processes within species remains largely unknown. By using a unique intercross chicken population based on parental lines with high divergence in cerebellum size, we compared the behavior of individuals repeatedly exposed to the same fear test (emergence test) early in life and after sexual maturity (eight trials per age group) with proportional cerebellum size and cerebellum neural density. While proportional cerebellum size did not predict the initial fear response of the individuals (trial 1), it did increasingly predict adult individuals response as the trials progressed. Our results suggest that proportional cerebellum size does not necessarily predict an individual's fear response, but rather the habituation process to a fearful stimulus. Cerebellum neuronal density did not predict fear behavior in the individuals which suggests that these effects do not result from changes in neuronal density but due to other variables linked to proportional cerebellum size which might underlie fear habituation.
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| 13. |
- Wierup, Martin, et al.
(författare)
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Biosafety considerations and risk reduction strategy for a new veterinary faculty building and teaching hospital in Sweden
- 2020
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Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This paper describes a hazard- and risk-based strategy and recommendations on relevant biosafety levels in facility design of a new veterinary faculty building including a veterinary medical teaching hospital. Both animal and human health were considered.Materials and methods: Agents listed in the regulatory frameworks on animal and human health were identified as the main potential hazards. Suggestions on biosafety level and facility design were based on the official risk grouping of those agents, the associated risk management procedures, and biosafety experiences from previous faculty buildings.Results and Discussion: It was suggested that VHC should not be designed for work with agents requiring facilities at biosafety levels 3 and 4, and that actions in cases of accidental exposure to notifiable infections should follow the regulatory requirements. Facilities requiring biosafety level 2 were identified from risk scenarios and transmission routes. Experiences from the first five years of operation revealed good prevention of spread of infection from patients in isolation facilities and successful elimination of Salmonella and MRSA from the large animal clinic.Conclusion: In order to avoid costly construction mistakes, an overall biosafety strategy should be formulated and used as guidance for architects and other relevant stakeholders designing facilities for the animal health sector. Regulatory requirements on infectious diseases must be complied with.
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| 14. |
- Chelcea, Ioana C., 1994-, et al.
(författare)
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Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols
- 2023
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 345
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Tidskriftsartikel (refereegranskat)abstract
- Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption. Variation in effects between chemicals are difficult to compare using nominal dose as toxicokinetic properties may vary. Toxicokinetic (TK) modeling is a means to estimate internal exposure concentration or dose at target and to enable extrapolation between experimental conditions and species, thereby improving hazard assessment of potential pollutants. In this study we advance currently existing TK models for ZFE with physiological ZFE parameters and novel experimental bisphenol data, a class of chemicals with suspected endocrine activity. We developed a five-compartment model consisting of water, plastic, chorion, yolk sack and embryo in which surface area and volume changes as well as the processes of biotransformation and blood circulation influence mass fluxes. For model training and validation, we measured internal concentrations in ZFE exposed individually to BPA, bisphenol AF (BPAF) and Z (BPZ). Bayesian inference was applied for parameter calibration based on the training data set of BPZ. The calibrated TK model predicted internal ZFE concentrations of the majority of external test data within a 5-fold error and half of the data within a 2-fold error for bisphenols A, AF, F, and tetrabromo bisphenol A (TBBPA). We used the developed model to rank the hazard of seven bisphenols based on predicted internal concentrations and measured in vitro estrogenicity. This ranking indicated a higher hazard for BPAF, BPZ, bisphenol B and C (BPB, BPC) than for BPA.
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| 15. |
- Strage, Emma, et al.
(författare)
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Insulin release from isolated cat islets of Langerhans
- 2024
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Ingår i: Domestic Animal Endocrinology. - : Elsevier. - 0739-7240 .- 1879-0054. ; 87
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Tidskriftsartikel (refereegranskat)abstract
- Feline diabetes mellitus is a common endocrine disease with increasing prevalence. It shows similarities with human type 2 diabetes and is characterized by insulin resistance and deficient insulin secretion. Moreover, cats and humans belong to the very few species that form amyloid depositions in the pancreatic islets. However, little is known about cat islet function and no studies have addressed insulin secretion from isolated islets ex vivo. The aim of this study was to establish a protocol for isolation of islets of Langerhans from pancreata of cats euthanized due to disease, and to evaluate insulin secretion responses to various physiological and pharmacological stimuli. Collagenase digestion of pancreatic tissue from 13 non-diabetic cats and two cats with diabetic ketoacidosis yielded individual islets surrounded by a layer of exocrine tissue that was reduced after two days in culture. Histological examination showed islet amyloid in pancreatic biopsies from most non-diabetic and in one diabetic cat. Islets from non-diabetic cats cultured at 5.5 mM glucose responded with increased insulin secretion to 16.7 mM glucose, 30 mM K+ and 20 µM of the sulfonylurea glipizide (2-3 times basal secretion at 3 mM glucose). The glucagon-like peptide-1 receptor agonist exendin-4 (100 nM) had no effect under basal conditions but potentiated glucose-triggered insulin release. Only one of nine islet batches from diabetic cats released detectable amounts of insulin, which was enhanced by exendin-4. Culture of islets from non-diabetic cats at 25 mM glucose impaired secretion both in response to glucose and K+ depolarization. In conclusion, we describe a procedure for isolation of islets from cat pancreas biopsies and demonstrate that isolated cat islets secrete insulin in response to glucose and antidiabetic drugs. The study provides a basis for future ex vivo studies of islet function relevant to the understanding of the pathophysiology and treatment of feline diabetes.
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| 16. |
- Einarsdottir, Sigrun, et al.
(författare)
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Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
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Tidskriftsartikel (refereegranskat)abstract
- Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
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| 17. |
- Peck, Charlie, et al.
(författare)
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Confidence among Veterinary Students to Perform Canine Orchiectomy : The Impact of Live Animal Surgical Clinical Training
- 2023
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Ingår i: Journal of Veterinary Medical Education. - : University of Toronto Press Inc. (UTPress). - 0748-321X .- 1943-7218. ; 50, s. 475-481
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Tidskriftsartikel (refereegranskat)abstract
- Canine orchiectomy (COE) is one of the most commonly performed procedures in small animal veterinary surgery.The aim of this study was to assess veterinary students’ confidence in performing this surgery in relation to their previous surgical experience of the procedure.The hypothesis was that confidence to perform canine orchiectomies among recent veterinary graduates increased when having participated in the procedure as part of practical surgical training. A cross-sectional survey was conducted and included 65 fifth-year veterinary graduate students at the Swedish University of Agriculture in Uppsala, Sweden.The survey investigated how differences in experience of COE affected students’ confidence to perform the procedure. Of the responding students, 24.6% had performed the procedure, 47.7% had observed the procedure live, and 27.7% had not seen nor performed the procedure.They were asked how confident they were to perform the procedure both with and without assistance. Data were compared using a non-parametric test (Mann–Whitney U test). The results showed a statistically significant increase in confidence to perform COEs in the group that had previously performed or observed COE compared with the group that had neither performed nor observed the procedure. In conclusion, veterinary students’ participation in COEs significantly contributed to their clinical confidence to perform the procedure
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| 18. |
- Högberg, Niclas
(författare)
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Sensing the worms : automated behaviour monitoring for detection of parasitism in grazing livestock
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastrointestinal nematodes (GIN) are common in grazing livestock and is a major cause of impaired health and productivity. Current control practices of GIN infections depend largely on the use of anthelmintic drugs. However, misuse of anthelmintic drugs has led to a widespread development of anthelmintic resistance. Behavioural monitoring has been suggested as a novel method to detect parasite infection in grazing livestock, enabling targeted (selective) treatment, where only infected groups or individual animals within a group are treated. The aim of this thesis was to investigate how multispecies GIN parasite infections affect behavioural patterns in grazing livestock on a group level using different on-animal sensors. The effect of subclinical GIN infection on activity and rumination patterns in first season grazing steers were investigated in contrasting groups during two grazing seasons, using different commercial sensors. The results indicate that untreated steers exposed to a higher GIN level had an increased lying time, lower activity level and affected rumination patterns over time, compared with dewormed steers. To enable the assessment of behavioural responses in lambs, the validity of two sensors for cattle for use in lambs were first evaluated. The effect of subclinical GIN infection on activity in lambs around weaning was then investigated in a replicated grazing trial with treated and untreated groups. The results indicate untreated lambs had a shorter daily lying time over time as well as a lower activity level, compared with dewormed lambs. In conclusion, this thesis supports that behavioural patterns are affected by subclinical GIN infections and the results demonstrate the potential use of automated behavioural observations as a diagnostic tool.
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| 19. |
- Roepstorff, Lars
(författare)
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The Development of a Standardized Protocol for Quantifying Equestrian Eventing Cross-Country Ground
- 2023
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Ingår i: Biomechanics (Switzerland). - 2673-7078. ; 3, s. 343-361
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Tidskriftsartikel (refereegranskat)abstract
- The ground has long been cited as a key contributing factor for injury risk in the cross-country phase of eventing. The current study aimed to develop a practically useful standardized protocol for measuring eventing cross country ground. Data collection was split into three phases: Phase 1 (Validation), Phase 2 (Expansion of data set), and Phase 3 (Threshold establishment). During Phase 1, data from nine event courses were collected using an Orono Biomechanical Surface Tester (OBST), Vienna Surface Tester (VST), Lang Penetrometer, Going Stick, and moisture meter. Using linear regression, 80% of the variability in cushioning measured with the OBST was predicted from moisture and VST measurements (p < 0.001). In Phase 2, objective data from 81 event courses and subjective assessments from 180 event riders were collected. In Phase 3, k-means cluster analysis was used to classify the courses into ten clusters based on average course measurements of moisture, cushioning, firmness, stiffness, depth, and coefficient of restitution. Based on cluster membership, course average subjective data (16 courses) were compared using a General Linear Model. Significant differences (p < 0.05) in subjective impact firmness (p = 0.038) and subjective cushioning (p = 0.010) were found between clusters. These data and cluster thresholds provide an event course baseline for future comparisons.
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| 20. |
- Sätter, Joanna K., et al.
(författare)
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Biomechanical variables in Icelandic horse riders and the effect on tölt performance : A pilot study
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:6 June
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Tidskriftsartikel (refereegranskat)abstract
- Aim To identify how riding rein direction (left and right) and rider asymmetry affect tölt performance in Icelandic horses. Methods Two horses were ridden in tölt by four riders on both left and right reins. Riders wore pressure insoles that measured the total absolute force (FAbs) and absolute force difference (FDiff) in their left and right feet in the stirrups. A 3D motion-analysis system recorded the degrees of side-to-side movement in the pelvis (RollP) and in the thoracolumbar region (RollT). Lateral advanced placement (LAP) and duty factor (DF) were calculated to determine tölt performance. One-way ANOVAs were used to assess the effect of rein direction on rider asymmetry variables (FAbs, FDiff, RollP and RollT) and tölt performance (LAP, DF) on a group level (n = 8). Within-subject Spearman rank correlations (ρ) were computed to determine the effect of rider asymmetry variables on tölt performance on an individual level. Results LAP was closer to 25% on the left rein compared to the right rein (mean difference: 1.8 ±1.2%; F(1,7) = 16.333; p = 0.005, η2p = 0.700). In addition, DF was lower on the left rein compared to the right rein (mean difference: 1.9±0.8%; F(1,7) = 41.299; p<0.001, η2p = 0.855). Individual relationships between RollT and LAP ranged from small negative to very large positive and reached significance for one rider (ρ = 0.730; p = 0.040). Individual relationships between RollP and DF ranged from very large negative to very large positive and reached significance for two riders (ρ = 0.731; p = 0.040; ρ = -0.723 p = 0.043). Conclusion Rein direction might influence tölt performance. Individual relationships between rider asymmetry and tölt performance were highly variable and reached significance in some instances, indicating that the relationship between rider asymmetry and tölt performance is highly individual. This type of biomechanical data can be used to provide valuable feedback to guide equestrians and coaches.
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| 21. |
- Rhodin, Marie, et al.
(författare)
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Timing of Vertical Head, Withers and Pelvis Movements Relative to the Footfalls in Different Equine Gaits and Breeds
- 2022
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Movement symmetry of the head and pelvis are used to measure lameness in horses in trot. Although head, pelvis and limb movements have been described, less is known about the temporal relationships between them. This information is needed to understand how the movements change with lameness. This is particularly relevant in gaited horses, such as the Icelandic horse that perform gaits such as tolt and pace, which are challenging to evaluate. This study used inertial measurement units to investigate head, withers and pelvis motion relative to limb movements in Icelandic, Warmblood and Iberian horses. Limb movements, together with vertical movements and lowest/highest positions of the head, withers and pelvis were calculated, and the relative timing of the events was compared across breeds. Additionally, data for tolt and pace were collected and evaluated in ridden Icelandic horses. For all gaits except walk and pace, the lowest/highest positions of the head/withers/pelvis were closely temporally related to midstance and hoof-off, respectively. Pelvic and withers total range of motion differed between all breeds. The Icelandic horses showed shorter stride duration and smaller movements of the upper body than the other breeds at trot, which may explain why lameness evaluation in this breed is challenging. Knowledge of vertical motion patterns of the axial body segments is a prerequisite for the development of algorithms used in automated detection of lameness. To date, the focus has been on the trot. This study investigates the temporal synchronization between vertical motion of the axial body segments with limb kinematic events in walk and trot across three popular types of sport horses (19 Warmbloods, 23 Iberians, 26 Icelandics) that are known to have different stride kinematics, and it presents novel data describing vertical motion of the axial body segments in tolting and pacing Icelandic horses. Inertial measurement unit sensors recorded limb kinematics, vertical motion of the axial body at all symmetrical gaits that the horse could perform (walk, trot, tolt, pace). Limb kinematics, vertical range of motion and lowest/highest positions of the head, withers and pelvis were calculated. For all gaits except walk and pace, lowest/highest positions of the pelvis and withers were found to be closely related temporally to midstance and start of suspension of the hind/fore quarter, respectively. There were differences in pelvic/withers range of motion between all breeds where the Icelandic horses showed the smallest motion, which may explain why lameness evaluation in this breed is challenging.
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| 22. |
- Adepu, Saritha, et al.
(författare)
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Salivary biglycan-neo-epitope-BGN262: A novel surrogate biomarker for equine osteoarthritic sub-chondral bone sclerosis and to monitor the effect of short-term training and surface arena
- 2023
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. Design: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N = 19) and OA horses (N = 9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluate the robustness of BGN262. Cohorts 2 (N = 5) & 3 (N = 7): Longitudinal studies of sampling during a short-term training exercise (sand-fibre) and a cross-over design of short-training exercise on 2 different riding arenas (sand and sand-fibre), respectively. Capillary western immunoassay was used to determine the BGN262 molecular size in a selection of saliva samples collected from cohort 1. Results: Cohort 1: Salivary BGN262 levels were significantly higher in the OA group. The Receiver operating characteristic curve analysis showed an area under the curve of 0.8304 [0.6386 to 1.022], indicating a good separation from the reference group. Cohorts 2 & 3: Salivary BGN262 levels significantly changed during the exercise on sand and sand-fibre arena, with a trend towards higher levels for sand-fibre. The size of the BGN262 fragment determined by Capillary western assay was 18 kDa. Conclusions: The data presented show saliva BGN262 levels as a novel biomarker in evaluating the influence of exercise, and interaction with riding arenas alongside assessing osteoarthritis severity.
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| 23. |
- Bergh, Anna
(författare)
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Part I of Finnish Agility Dog Survey: Training and Management of Competition-Level Agility Dogs
- 2022
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Information on training, competition, and management of agility dogs is sparse. To decrease this knowledge gap, Finnish owners and handlers of competition-level agility dogs completed an online questionnaire to describe the agility routines of their dog during one injury-free year. Additional information on competition routines was retrieved from the national competition results database. Typically, competition-level agility dogs trained agility once or twice a week and competed two runs a month. The median total weekly training time was 18 min. Usual speed over the competition course was 4.3 m/s. Artificial turf, with or without filling, and dirt surfaces are used most often. Dogs are warmed up before and cooled down after agility performance. Most dogs visit a massage therapist, physiotherapist, osteopath or other professionals of musculoskeletal care at least every three months. Many dogs undergo conditioning exercises, although often less often than every two weeks. Additionally, agility dogs are walked for a total of 1.5 h a day. Dogs competing at the highest levels competed more but trained less than dogs at lower levels. This is the first investigation of agility-related routines in competing agility dogs. Knowledge regarding training, competition, and management routines of agility dogs is lacking. Through a retrospective online questionnaire, Finnish owners and handlers of 745 competition-level agility dogs provided information on training routines and management of these dogs during one year free of agility-related injuries. Competition routines were collected from the national competition results database. Most dogs trained agility 1-2 times a week, with a median active training time of 18 min a week. Dogs competed in a median of 2.1 runs per month at a speed of 4.3 m/s. Common field surfaces were different types of artificial turfs and dirt surface. Warm-up and cool-down were established routines, and 62% of dogs received regular musculoskeletal care. Moreover, 77% of dogs underwent conditioning exercises, but their frequency was often low. Additionally, dogs were walked for a median of 1.5 h daily. Pearson's chi-squared and Kruskal-Wallis tests were used to evaluate the association between a dog's competition level and training and competition variables. A dog's competition level was associated with competition (p < 0.001) and training frequency (p < 0.001); dogs at higher levels compete more but train less than dogs at lower levels. This study provides information on training, competition, and management routines of competing agility dogs.
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| 24. |
- Dubbelboer, Ilse R, et al.
(författare)
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Gastrointestinal mucus in dog : Physiological characteristics, composition, and structural properties
- 2022
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 173, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog.Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology.GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure.In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.
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| 25. |
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| 26. |
- Gau, Rémi, et al.
(författare)
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Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
- 2021
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Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
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Tidskriftsartikel (refereegranskat)abstract
- Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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| 27. |
- Johansson, Lisa, et al.
(författare)
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A metabolomics perspective on 2 years of high-intensity training in horses
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The plasma metabolomic profile of elite harness horses subjected to different training programmes was explored. All horses had the same training programme from 1.5 until 2 years of age and then high-intensity training was introduced, with horses divided into high and low training groups. Morning blood samples were collected at 1.5, 2, 2.5 and 3.5 years of age. The plasma was analysed using targeted absolute quantitative analysis and a combination of tandem mass spectrometry, flow-injection analysis and liquid chromatography. Differences between the two training groups were observed at 2 years of age, when 161 metabolites and sums and ratios were lower (e.g. ceramide and several triglycerides) and 51 were higher (e.g. aconitic acid, anserine, sum of PUFA cholesteryl esters and solely ketogenic AAs) in High compared with low horses. The metabolites aconitic acid, anserine, leucine, HArg synthesis and sum of solely ketogenic AAs increased over time, while beta alanine synthesis, ceramides and indole decreased. Therefore high-intensity training promoted adaptations linked to aerobic energy production and amino acid metabolism, and potentially also affected pH-buffering and vascular and insulin responses.
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| 28. |
- Johansson, Lisa, et al.
(författare)
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Reduced high-intensity training distance in growing horses had no effect on IGF-1 concentrations, but training onset interrupted time-dependent IGF-1 decline
- 2022
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Ingår i: Comparative Exercise Physiology. - : Wageningen Academic Publishers. - 1755-2540 .- 1755-2559. ; 18:3, s. 201-209
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated plasma insulin like growth factor (IGF)-1 concentrations in 16 young Standardbred horses introduced to systematic high-intensity training at two different levels of intensity. Growth and locomotion asymmetry and correlations between these and plasma IGF-1 concentrations were also examined. From September as 1-year olds to March as 2-year olds (Period 1), all horses were subjected to the same submaximal training program. In March (start of Period 2), the horses were divided into two groups (n=8) and one group was introduced to regular high-intensity training. The other group was introduced to a program where the high-intensity exercise distances were reduced by 30%. These two training programs were maintained for the remaining 21 months of the study (Periods 2, 3, and 4). There was no effect of training group on plasma IGF-1 concentrations. A continuous decline in IGF-1 levels was observed throughout the study (P<0.0001), with one notable interruption in Period 2 when the IGF-1 concentration remained at the level seen at the start of Period 1. Growth rate of body length was equally high in Periods 1 and 2 (P>0.05). Front and hind limb asymmetry was elevated in Period 2 compared with Period 1. There were positive correlations between IGF-1 concentrations and changes in body condition score, and a negative correlation between IGF-1 concentration and weight. These results indicate that introduction to high-intensity training induces IGF-1 release in horses, but that a 30% difference in the distances used in high-intensity training does not affect IGF-1 levels. The temporary interruption in decline in IGF-1 release with the onset of high-intensity training may influence growth pattern and locomotion asymmetry, but further studies are needed to assess causality.
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| 29. |
- Kjörk Granström, Miriam, et al.
(författare)
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Evaluation of forelimb gait variation overground at a walk in sound and lame dogs using a combination of diagnostic techniques
- 2024
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Ingår i: Acta Veterinaria Scandinavica. - 0044-605X .- 1751-0147. ; 66
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Tidskriftsartikel (refereegranskat)abstract
- Background Kinetic and kinematic gait analysis is increasingly practised as a part of lameness evaluation in dogs. The aim of this study was to examine the normal short- and long-term variation in forelimb gait in sound control dogs (CD) at a walk using seven selected variables of objective kinetic and kinematic gait analyses. Also, to compare the findings in CD to a group of forelimb lame dogs with elbow osteoarthritis (OAD). An additional aim was to test a kinetic based graphic method for lameness detection; symmetry squares (SS). A prospective longitudinal study was carried out on client owned CD and OAD. Clinical and orthopaedic evaluations were performed to ensure soundness and detect and grade lameness. Seven kinetic and kinematic variables and SS were tested for lameness evaluation. The CD were divided into two subgroups, CD1 and CD2, and examined twice: CD1 with two months interval and CD2 with 3-4 h interval. The OAD group was evaluated once and compared to the CD groups' first examination.Results Thirteen CD and 19 OAD were included. For CD1 and CD2, there were no significant differences in any examined variable between examination occasions. Total peak force/impulse symmetry and fore-hind peak force/impulse symmetry differed significantly between OAD and CD. Symmetry squares had a 74% agreement to subjective orthopaedic evaluations.Conclusions In CD, no difference in the examined variables was seen between examination occasions. Four out of seven objective variables differed significantly between CD and OAD. The graphic SS method might have diagnostic potential for lameness detection, making it possible to detect a shift from lame to non-lame limbs. Potentially, this might be especially helpful in bilaterally lame dogs, which often represent a clinical challenge in lameness evaluation.
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| 30. |
- Leclercq, Anna, et al.
(författare)
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Evaluation of feedback methods for improved detection of hindlimb lameness in horses among riding instructors and trainers
- 2022
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Lameness, a wellknown issue in sport horses, impedes performance and impairs welfare. Early detection of lameness is essential for horses to receive needed treatment, but detection of hindlimb lameness is challenging. Riding instructors and trainers observe horses in motion in their daily work and could contribute to more efficient lameness detection. In this cross-sectional and prospective study, we evaluated the ability of riding instructors and trainers to assess hindlimb lameness. We also evaluated different feedback methods for improved lameness detection. For the cross-sectional part, n = 64 riding instructors and trainers of varying level and n = 23 high-level trainers were shown 13 videos of trotting horses, lameness degree: 0-3.5 (test 1) and tasked with classifying the horses as sound, left hindlimb lame, or right hindlimb lame. For the prospective part, the riding instructors and trainers of varying levels were randomly allocated to three different groups (a, b, c) and given 14 days of feedback-based, computer-aided training in identifying hindlimb lameness, where they assessed 13 videos (of which three were repeated from test 1) of horses trotting in a straight line. Participants in groups a-c received different feedback after each video (group a: correct answer and re-viewing of video at full and 65% speed; group b: correct answer, re-viewing of video at full and 65% speed, narrator providing explanations; group c: correct answer and re-viewing of video at full speed). After computer-aided training, the participants were again subjected to the video test (test 2). Participants also provided background information regarding level of training etcetera. Effects of participants' background on results were analyzed using analysis of variance, and effects of the different feedback methods were analyzed using generalized estimation equations. On test 1, 44% (group a), 48% (b), 46% (c), and 47% (high-level trainers) of horses were correctly classified. Group a participants significantly improved their test score, both with (p < 0.0001) and without (p = 0.0086) inclusion of repeated videos. For group c, significant improvement was only seen with inclusion of repeated videos (p = 0.041). For group b, no significant improvement was seen (p = 0.51). Although test 2 scores were low, computer-aided training may be useful for improving hindlimb lameness detection.
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| 31. |
- Olsson Lindvall, Martina, et al.
(författare)
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Comparison of DNA Methylation Profiles of Hemostatic Genes between Liver Tissue and Peripheral Blood within Individuals
- 2021
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 121:5, s. 573-583
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation has become increasingly recognized in the etiology of complex diseases, including thrombotic disorders. Blood is often collected in epidemiological studies for genotyping and has recently also been used to examine DNA methylation in epigenome-wide association studies. DNA methylation patterns are often tissue-specific, thus, peripheral blood may not accurately reflect the methylation pattern in the tissue of relevance. Here, we collected paired liver and blood samples concurrently from 27 individuals undergoing liver surgery. We performed targeted bisulfite sequencing for a set of 35 hemostatic genes primarily expressed in liver to analyze DNA methylation levels of >10,000 cytosine-phosphate-guanine (CpG) dinucleotides. We evaluated whether DNA methylation in blood could serve as a proxy for DNA methylation in liver at individual CpGs. Approximately 30% of CpGs were nonvariable and were predominantly hypo- (<25%) or hypermethylated (>70%) in both tissues. While blood can serve as a proxy for liver at these CpGs, the low variability renders these unlikely to explain phenotypic differences. We therefore focused on CpG sites with variable methylation levels in liver. The level of blood-liver tissue correlation varied widely across these variable CpGs; moderate correlations (0.5 <= r <0.75) were detected for 6% and strong correlations ( r 0.75) for a further 4%. Our findings indicate that it is essential to study the concordance of DNA methylation between blood and liver at individual CpGs. This paired blood-liver dataset is intended as a resource to aid interpretation of blood-based DNA methylation results.
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| 32. |
- Persson-Sjodin, Emma, et al.
(författare)
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Withers vertical movement symmetry is useful for locating the primary lame limb in naturally occurring lameness
- 2024
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Ingår i: Equine Veterinary Journal. - : WILEY. - 0425-1644 .- 2042-3306. ; 56:1, s. 76-88
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDuring orthopaedic assessment of lame horses, a head nod is commonly present in both primary forelimb and hindlimb lame horses. Additional motion metrics that could assist clinicians in correctly differentiating between these two scenarios would be of great clinical value. ObjectivesThe primary objective of this study was to examine whether withers movement asymmetry can be used in a clinical setting to distinguish primary forelimb lameness from compensatory head movement asymmetry due to primary hindlimb lameness. Study designRetrospective, multicentre study. MethodsMovement asymmetry of head, withers and pelvis was measured using multi-camera optical motion capture, as part of routine lameness investigations at four European equine hospitals. Vertical movement asymmetry parameters from 317 horses trotting in a straight line were compared before and after successful diagnostic analgesia of a single limb. Descriptive statistics, t-tests and linear models were used to analyse the data. ResultsIn forelimb lame horses, 80%-81% showed head and withers asymmetry both indicating lameness in the same forelimb. In hindlimb lame horses, 69%-72% showed head asymmetry ipsilateral to the lame hindlimb and withers asymmetry diagonal to the lame hindlimb, thus, head and withers asymmetry indicated lameness in different forelimbs. A large (>15 mm) compensatory head nod was seen in 28%-31% of the hindlimb lame horses. In 89%-92% of these, head and withers asymmetry indicated lameness in different forelimbs. Withers asymmetry decreased linearly with reduced head or pelvic asymmetry for both forelimb and hindlimb lame horses. Main limitationsCompensatory strategies were evaluated on group level to identify common patterns, potentially ignoring uncommon individual strategies. ConclusionsWithers vertical movement asymmetry metrics can be useful in helping to locate the primary lame limb during quantitative lameness assessment. Head and withers movement asymmetry parameters generally indicate the same forelimb in forelimb lame horses, but different forelimbs in hindlimb lame horses.
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| 33. |
- Sajib, Mursalin, 1987, et al.
(författare)
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Effect of antioxidants on lipid oxidation in herring (Clupea harengus) co-product silage during its production, heat-treatment and storage
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Provided high product quality, ensilaging can be used to valorize fish filleting co-products into a silage suitable for food applications. However, a documented challenge for products from hemoglobin-rich fish raw materials is the high susceptibility to lipid oxidation, calling for stabilization by antioxidants. In a comparison among different rosemary-containing antioxidants and isoascorbic acid, we here found that the commercial mixture Duralox MANC-213 (MANC) provided the best protection against peroxide value and 2-thiobarbituric acid reactive substances (TBARS) development during ensilaging of herring filleting co-products (0–7 days, 22 °C), and also during subsequent heat-treatment (30 min, 85 °C). Increasing MANC concentration from 0.25 and 0.75 to 1.25% lowered TBARS values from 43.53 and 25.12 to 18.04 µmole TBARS/Kg silage, respectively, after 7 days of ensilaging. During storage at 4 °C/22 °C in presence of MANC, 1.25% provided the highest protection with 87–90% and 66–73% lower TBARS, at 4 °C and 22 °C, respectively, at 6 months compared to the controls. At this time point, heat-treated silages had lower protein degree of hydrolysis and free amino acids values than the non-heat-treated one. Regardless of antioxidant addition, total volatile basic nitrogen (TVB-N) formation still increased during the storage, but, overall, TVB-N values in silages were below the acceptable limit of 30 mg TVB-N/100 g fish for human consumption. Together with lipid oxidation data, this suggests that herring silage produced in presence of antioxidants can be used both for high-quality feed and food applications.
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| 34. |
- Sjöström, Karin, et al.
(författare)
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Antimicrobial Resistance Patterns in Organic and Conventional Dairy Herds in Sweden
- 2020
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Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring antimicrobial resistance (AMR) and use (AMU) is important for control. We used Escherichia coli from healthy young calves as an indicator to evaluate whether AMR patterns differ between Swedish organic and conventional dairy herds and whether the patterns could be related to AMU data. Samples were taken twice, in 30 organic and 30 conventional dairy herds. Selective culturing for Escherichia coli, without antibiotics and with nalidixic acid or tetracycline, was used to estimate the proportions of resistant isolates. Microdilution was used to determine the minimum inhibitory concentrations (MICs) for thirteen antimicrobial substances. AMU data were based on collection of empty drug packages. Less than 8% of the bacterial growth on non-selective plates was also found on selective plates with tetracycline, and 1% on plates with nalidixic acid. Despite some MIC variations, resistance patterns were largely similar in both periods, and between organic and conventional herds. For most substances, only a few isolates were classified as resistant. The most common resistances were against ampicillin, streptomycin, sulfamethoxazole, and tetracycline. No clear association with AMU could be found. The lack of difference between organic and conventional herds is likely due to a generally good animal health status and consequent low AMU in both categories.
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| 35. |
- Wilhelm, Franziska R., et al.
(författare)
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Iohexol-based measurement of intestinal permeability in birds
- 2020
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Ingår i: Journal of Exotic Pet Medicine. - : Elsevier. - 1557-5063. ; 34, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species.Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration.Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 µg/ml in pigeons, 12.97 µg/ml in chickens, 14.24 µg/ml in cockatiels, and 47.81 µg/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 µg/ml in pigeons, 21.59 µg/ml in chickens, 32.03 µg/ml in cockatiels, and 55.96 µg/ml in falcons.Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability.
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| 36. |
- Younis, Shady, et al.
(författare)
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Ablation of ZC3H11A causes early embryonic lethality and dysregulation of metabolic processes
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:23
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Tidskriftsartikel (refereegranskat)abstract
- ZC3H11A (zinc finger CCCH domain-containing protein 11A) is a stress-induced mRNA-binding protein required for efficient growth of nuclear-replicating viruses. The cellular functions of ZC3H11A during embryonic development are unknown. Here, we report the generation and phenotypic characterization ofZc3h11a knockout (KO) mice. Heterozygous null Zc3h11a mice were born at the expected frequency without distinguishable phenotypic differences compared with wild-type mice. In contrast, homozygous null Zc3h11a mice were missing, indicating that Zc3h11a is crucial for embryonic viability and survival. Zc3h11a -/- embryos were detected at the expected Mendelian ratios up to late preimplantation stage (E4.5). However, phenotypic characterization at E6.5 revealed degeneration of Zc3h11a( -/-) embryos, indicating developmental defects around the time of implantation. Transcriptomic analyses documented a dysregulation of glycolysis and fatty acid metabolic pathways in Zc3h11a(-/-) embryos at E4.5. Proteomic analysis indicated a tight interaction between ZC3H11A and mRNA-export proteins in embryonic stem cells. CLIP-seq analysis demonstrated that ZC3H11A binds a subset of mRNA transcripts that are critical for metabolic regulation of embryonic cells. Furthermore, embryonic stem cells with an induced deletion of Zc3h11a display an impaired differentiation toward epiblast-like cells and impaired mitochondrial membrane potential. Altogether, the results show that ZC3H11A is participating in export and posttranscriptional regulation of selected mRNA transcripts required to maintain metabolic processes in embryonic cells. While ZC3H11A is essential for the viability of the early mouse embryo, inactivation of Zc3h11a expression in adult tissues using a conditional KO did not lead to obvious phenotypic defects.
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| 37. |
- Parv, Kristel
(författare)
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Macrophages and neutrophils in tissue homeostasis and recovery from ischemic injury
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neutrophils and macrophages have functions beyond protection against pathogens. The overall aim of the work presented in this thesis was to identify novel tasks for these innate immune cells in maintaining homeostasis. In the studies presented here, we explored macrophage roles in tissue recovery from ischemic injury and post-natal tissue development, and the origin and recruitment mechanisms of pro-angiogenic neutrophils (PANs) to the site of ischemic injury.In Study I, it was shown that perivascular macrophages at sites of ischemic injury adopt characteristics of mural cell identity. Combining genetic heritable fate mapping of macrophages with single-cell RNA-sequencing, we were able to demonstrate that macrophages downregulated the expression of myeloid markers, and upregulated those of mural cells. Depletion of macrophages during tissue healing demonstrated that macrophages also adopt important mural cell functions that are crucial for blood vessel maturation after ischemic injury. In Study II, it was shown that perivascular macrophages form cuff-like structures around vessels in the ischemic muscle following ischemia. Using genetically modified mouse models, we showed that these macrophages regulate bloodflow in an inducible NO Synthase (iNOS)-dependent manner, and this could be therapeutically targeted to improve tissue healing through local delivery of plasmid-encoded C-X-C Motif Chemokine Ligand 12 (CXCL12). In Study III, it was shown that recruitment of PANs to the site of ischemic injury is dependent on CD49d signalling, and the spleen contains a peripheral reservoir of PANs which is crucial for achieving adequate accumulation of PANs at the site of ischemic injury. We also showed that the release of splenic PANs in response to ischemic injury relies on sympathetic signalling and downregulation of CXCL12α in the splenic red pulp.In Study IV, it was shown that pancreatic tissue-resident macrophages are important for post-natal islet development, as depletion of macrophages using clodronate liposomes led to impaired glucose tolerance in adult mice. Further, neonatal infection with S. aureus led to reduced number of pancreatic macrophages and interfered with normal post-natal β cell development, leading to impaired glucose tolerance. In summary, the work presented here expands our understanding on the various roles of macrophages during ischemic injury and tissue development, and significantly advances our understanding of the origins and recruitment mechanisms of pro-angiogenic neutrophils during ischemic injury.
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| 38. |
- Vossen, Laura E., et al.
(författare)
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Sex-Specific Effects of Acute Ethanol Exposure on Locomotory Activity and Exploratory Behavior in Adult Zebrafish (Danio rerio)
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The zebrafish (Danio rerio) is an established model organism in pharmacology and biomedicine, including in research on alcohol use disorders and alcohol-related disease. In the past 2 decades, zebrafish has been used to study the complex effects of ethanol on the vertebrate brain and behavior in both acute, chronic and developmental exposure paradigms. Sex differences in the neurobehavioral response to ethanol are well documented for humans and rodents, yet no consensus has been reached for zebrafish. Here, we show for the first time that male zebrafish of the AB strain display more severe behavioral impairments than females for equal exposure concentrations. Adult zebrafish were immersed in 0, 1 or 2% (v/v) ethanol for 30 min, after which behavior was individually assessed in the zebrafish Multivariate Concentric Square Field (TM) (zMCSF) arena. Males exposed to 2% ethanol showed clear signs of sedation, including reduced activity, increased shelter seeking and reduced exploration of shallow zones. The 1% male group displayed effects in the same direction but of smaller magnitude; this group also explored the shallow areas less, but did not show a general reduction in activity nor an increase in shelter seeking. By contrast, 1 and 2% exposed females showed no alterations in explorative behavior. Females exposed to 2% ethanol did not display a general reduction in activity, rather activity gradually increased from hypoactivity to hyperactivity over the course of the test. This mixed stimulatory/depressant effect was only quantifiable when locomotory variables were analyzed over time and was not apparent from averages of the whole 30-min test, which may explain why previous studies failed to detect sex-specific effects on locomotion. Our results emphasize the importance of explicitly including sex and time as factors in pharmacological studies of zebrafish behavior. We hypothesize that the lower sensitivity of female zebrafish to ethanol may be explained by their greater body weight and associated larger distribution volume for ethanol, which may render lower brain ethanol concentrations in females.
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| 39. |
- Baruah, Kartik
(författare)
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The Combined Use of Pediococcus pentosaceus and Fructooligosaccharide Improves Growth Performance, Immune Response, and Resistance of Whiteleg Shrimp Litopenaeus vannamei Against Vibrio parahaemolyticus
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we evaluated the effect of probiotic bacteria Pediococcus pentosaceus supplemented at different inclusion levels in a control diet [basal diet containing 0.5% fructooligosaccharide (FOS)] on the growth performance, feed conversion ratio, immune response, and the disease resistance of whiteleg shrimp Litopenaeus vannamei juveniles against Vibrio parahaemolyticus. A control diet with 0.5% FOS but without P. pentosaceus supplementation (Control) was prepared. In addition, three other test diets were also formulated: control diet supplemented with P. pentosaceus at (i) 1 x 10(6) cfu g(-1) diet (P1), (ii) 1 x 10(7) cfu g(-1) diet (P2), or (iii) 1 x 10(8) cfu g(-1) diet (P3). After a 60-day feeding trial, the experimental shrimps were challenged with V. parahaemolyticus. The results showed that dietary supplementation of P. pentosaceus significantly improved the growth performance and immune responses of L. vannamei juveniles. The juveniles that were fed with a P2 or P3 diet recorded the maximum increase in the final body weight, final length, weight gain, and survival rate. The total hemocyte counts, phenoloxidase, and lysozyme activity of shrimp fed with either of these two diets were significantly enhanced. The results also showed that juveniles fed with a P2 or P3 diet exhibited significantly lower mortality when challenged with V. parahaemolyticus. Overall results suggested that a combination of P. pentosaceus at the inclusion level of 1 x 10(7) cfu g(-1) diet (P2) and 0.5% FOS could be considered as a potential synbiotic formulation for improving the growth, health, and robustness of L. vannamei.
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| 40. |
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| 41. |
- Höglund, Johan
(författare)
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Occurrence of gastrointestinal nematodes in lambs in Norway, as assessed by copromicroscopy and droplet digital polymerase chain reaction
- 2024
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Ingår i: Acta Veterinaria Scandinavica. - 0044-605X .- 1751-0147. ; 66
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Tidskriftsartikel (refereegranskat)abstract
- Background Gastrointestinal nematodes (GINs) have a major impact on sheep production, health, and welfare worldwide. Norway is no exception, but there are only a few studies on the prevalence of GINs in Norwegian sheep. The aim of this study was to investigate the current occurrence of the most important nematodes in sheep flocks in Norway. Faecal samples were collected from flocks in 2021/2022, mainly from three geographical regions in Norway, i.e., northern, eastern, and western. In each of 134 flocks included, individual samples from 10 lambs (autumn) were pooled. Third stage larvae (L3) were cultivated and harvested (Baermann method) from the pooled samples. The DNA was then extracted and further analysed using droplet digital PCR (ddPCR). This enables assessment of the proportions of the three most important nematode species/genera, i.e., H. contortus, T. circumcincta, and Trichostrongylus. The fractional abundance/relative proportion of each species/genus was assessed by performing duplex assays with universal strongyle and species/genus-specific primers and probe sets. In addition, the occurrence of Nematodirus eggs was assessed by standard faecal egg counts (i.e., McMaster method). Results Of the 134 flocks sampled, 24 were from the northern region, 31 from eastern, and 71 from western Norway. In addition, some flocks from central (n = 7), and southern (n = 1) Norway were included. Among the sampled flocks, T. circumcincta occurred most commonly (94%), followed by H. contortus (60%) and Trichostrongylus (55%), and Nematodirus (51%). In general, mixed infections were observed, with 38% and 18% of flocks infected with three or all four genera, respectively. Conclusions The results of this study indicate that GINs are widespread in Norway. Teladorsagia circumcincta seems to be present in most flocks based on this screening. Moreover, the results show that Nematodirus spp. infect lambs throughout the country, predominantly N. battus, and indicate that this nematode has become more abundant, which could lead to an increase in nematodirosis.
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| 42. |
- Riihimäki, Miia, et al.
(författare)
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Single-cell transcriptomics delineates the immune cell landscape in equine lower airways and reveals upregulation of FKBP5 in horses with asthma.
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1, s. 16261-
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Tidskriftsartikel (refereegranskat)abstract
- Equine asthma (EA) is a heterogenous, complex disease, with a significant negative impact on horse welfare and performance. EA and human asthma share fundamental similarities, making EA a useful model for studying the disease. One relevant sample type for investigating chronic lung inflammation is bronchoalveolar lavage fluid (BALF), which provides a snapshot of the immune cells present in the alveolar space. To investigate the immune cell landscape of the respiratory tract in horses with mild-to-moderate equine asthma (mEA) and healthy controls, single-cell RNA sequencing was conducted on equine BALF cells. We characterized the major immune cell populations present in equine BALF, as well as subtypes thereof. Interestingly, the most significantly upregulated gene discovered in cases of mEA was FKBP5, a chaperone protein involved in regulating the activity of the glucocorticoid receptor.
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| 43. |
- Egenvall, Agneta, et al.
(författare)
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Roll And Pitch of the Rider's Pelvis During Horseback Riding at Walk on a Circle
- 2022
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Ingår i: Journal of Equine Veterinary Science. - : Elsevier BV. - 0737-0806 .- 1542-7412. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- The study investigated between-rider differences in pelvic roll and pitch motion during horseback riding as the horse walked around circles without rein contact (walk on long reins), with rein contact, and with moderate collection. Ten horses were ridden by five riders on left and right 10 m circles, in a partly crossed design, yielding 14 trials. Each trial included each of the three walk variations in both directions. Riders wore an inertial measurement unit (IMU), logging at 100 Hz, dorsally on the pelvis. Pelvic roll and pitch data were split into strides based on data from IMU-sensors on the horse's hind cannons. Data were analyzed using signal decomposition into the fundamental frequency (the stride frequency) and its first two harmonics. Mixed models accounting for the type of walk were used to analyze how riders differed in roll and pitch pelvic motion in two ways: comparing amplitudes of the frequency components and comparing whole stride mean data. Graphically pelvic pitch showed substantial timing and amplitude differences between riders, and this was confirmed statistically. Pelvic roll timing was similar, but amplitude varied between the riders, both graphically and statistically. Individual rider patterns tended to persist across different horses and all exercises. These results suggest that exercises at walk can be ridden with different pelvis pitch timing, a fact that has so far not been discussed in the equestrian literature. Whether pelvic pitch timing affects the horse's performance remains to be investigated. (c) 2021 Published by Elsevier Inc.
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| 44. |
- Cerritelli, Susana M, et al.
(författare)
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High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford Academic. - 0305-1048 .- 1362-4962. ; 48:8, s. 4274-4297
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Tidskriftsartikel (refereegranskat)abstract
- Cellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) into DNA. RNase H2-initiated ribonucleotide excision repair (RER) efficiently removes single rNMPs in genomic DNA. However, processing of rNMPs by Topoisomerase 1 (Top1) in absence of RER induces mutations and genome instability. Here, we greatly increased the abundance of genomic rNMPs in Saccharomyces cerevisiae by depleting Rnr1, the major subunit of ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides. We found that in strains that are depleted of Rnr1, RER-deficient, and harbor an rNTP-permissive replicative Pol mutant, excessive accumulation of single genomic rNMPs severely compromised growth, but this was reversed in absence of Top1. Thus, under Rnr1 depletion, limited dNTP pools slow DNA synthesis by replicative Pols and provoke the incorporation of high levels of rNMPs in genomic DNA. If a threshold of single genomic rNMPs is exceeded in absence of RER and presence of limited dNTP pools, Top1-mediated genome instability leads to severe growth defects. Finally, we provide evidence showing that accumulation of RNA/DNA hybrids in absence of RNase H1 and RNase H2 leads to cell lethality under Rnr1 depletion.
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| 45. |
- Malmström, Annika, 1957-, et al.
(författare)
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Do we really know who has an MGMT methylated glioma? : results of an international survey regarding use of MGMT analyses for glioma
- 2020
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Ingår i: Neuro-Oncology Practice. - Oxford : Oxford University Press. - 2054-2577 .- 2054-2585. ; 7:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.Methods: We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.Results: The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Conclusion: Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.
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| 46. |
- Maric, Ivana, et al.
(författare)
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Sex and Species Differences in the Development of Diet-Induced Obesity and Metabolic Disturbances in Rodents.
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Prevalence and health consequences of obesity differ between men and women. Yet, most preclinical studies investigating the etiology of obesity have, to date, been conducted in male rodents. Notably, diet is a major determinant of obesity, but sex differences in rodent models of diet-induced obesity, and the mechanisms that underlie such differences, are still understudied. Here, we aim to determine whether time course and characteristics of diet-induced obesity differ between sexes in rats and mice, and to investigate the potential causes of the observed divergence. To achieve this, we offered the most commonly tested rodents of both sexes, SD rats and C57BL/6 mice, a free choice of 60 % high-fat diet (HFD) and regular chow; body weight, food intake, fat mass, brown adipose responses, locomotor activity and glucose tolerance were assessed in a similar manner in both species. Our results indicate that overall diet-induced hyperphagia is greater in males but that females display a higher preference for the HFD, irrespective of species. Female rats, compared to males, showed a delay in diet-induced weight gain and less metabolic complications. Although male rats increased brown adipose tissue thermogenesis in response to the HFD challenge, this was not sufficient to counteract increased adiposity. In contrast to rats, female and male mice presented with a dramatic adiposity and impaired glucose tolerance, and a decreased energy expenditure. Female mice showed a 5-fold increase in visceral fat, compared to 2-fold increase seen in male mice. Overall, we found that male and female rodents responded very differently to HFD challenge, and engaged different compensatory energy expenditure mechanisms. In addition, these sex differences are divergent in rats and mice. We conclude that SD rats have a better face validity for the lower prevalence of overweight in women, while C57BL/6 mice may better model the increased prevalence of morbid obesity in women.
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| 47. |
- Nijs, Jo, et al.
(författare)
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Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
- 2020
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Ingår i: Expert Opinion on Therapeutic Targets. - : Informa UK Limited. - 1472-8222 .- 1744-7631. ; 24:8, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Few treatment programs for chronic pain nowadays take a dietary pattern or adipose status into account. Areas covered An important role of neuroinflammation in chronic pain is now well established, at least in part due to increased central nervous system glial activation. Based on preclinical studies, it is postulated that the interaction between nutrition and central sensitization is mediated via bidirectional gut-brain interactions. This model of diet-induced neuroinflammation and consequent central sensitization generates a rationale for developing innovative treatments for patients with chronic pain. Methods: An umbrella approach to cover the authors' expert opinion within an evidence-based viewpoint. Expert opinion A low-saturated fat and low-added sugar dietary pattern potentially decreases oxidative stress, preventing Toll-like receptor activation and subsequent glial activation. A low-saturated fat and low-added sugar diet might also prevent afferent vagal nerve fibers sensing the pro-inflammatory mediators that come along with a high-(saturated) fat or energy-dense dietary pattern, thereby preventing them to signal peripheral inflammatory status to the brain. In addition, the gut microbiota produces polyamines, which hold the capacity to excite N-methyl-D-aspartate receptors, an essential component of the central nervous system sensitization. Hence, a diet reducing polyamine production by the gut microbiota requires exploration as a therapeutic target for cancer-related and non-cancer chronic pain.
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| 48. |
- Zhu, Yajing, et al.
(författare)
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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial
- 2024
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 204:2, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.MethodsIn the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.ResultsNo association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.ConclusionsTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.Trial registrationClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.
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| 49. |
- Aboshady, Hadeer Moursy
(författare)
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Genomic variation and molecular mechanisms of the host response to gastrointestinal nematodes in small ruminants
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastrointestinal nematode (GIN) infections are one of the major constrains for sheep and goat production worldwide. One of the promising control strategies is the genetic selection for resistant animals as there are no issues due to anthelmintic resistance and it aligns to demands for chemical-free food. Exploring possible phenotypic and genomic markers that could be used in breeding scheme besides understanding the mechanisms responsible for resistance were the main goals of this thesis. Thesis consists of General introduction, a brief description of GIN biology and methods to control GIN with focus on phenotypic and genomic markers, four papers and General discussion. In paper Ⅰ, a systematic review and meta-analysis were conducted to re-analyse and summarize the findings on immunoglobulins response to GIN in the literature and discuss the potential to use immunoglobulins as biomarkers of the host resistance. A conceptual model summarizing the role of immunoglobulins in resistance to GIN is proposed. In paper Ⅱ, transcriptome profiling of the abomasal mucosa and lymph node tissues were compared between non-infected, resistant and susceptible Creole goats experimentally infected with Haemonchus contortus. Results indicated that the maintenance of the integrity of the mucosa has probably the priority for the host at late infection stage. In paper Ⅲ, the dynamics of the response of the abomasal mucosa of resistant and susceptible Creole goats experimentally infected with H. contortus were compared. The immune response was activated through many relevant pathways including the Th1 immune response at different time post-infection. Interestingly, the results showed a simultaneous time series activation of Th2 related genes in resistant compared to susceptible kids. In paper Ⅳ, the genomic variants of Creole goats resistant and susceptible to H. contortus were discovered from RNAsequencing data at four different times post-infection. Single nucleotide polymorphisms, insertions and deletions that distinguish the resistant and the susceptible groups were identified and characterized through functional analysis. The T cell receptor signalling pathway was one of the top significant pathways that distinguish the resistant from the susceptible group with genomic variants in 78% of genes in this pathway.
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| 50. |
- Braganca, F. M. Serra, et al.
(författare)
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Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.
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