| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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| 7. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 8. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 9. |
- Roswall, N., et al.
(författare)
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Long-Term Exposure to Transportation Noise and Risk of Incident Stroke: A Pooled Study of Nine Scandinavian Cohorts
- 2021
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through linkage to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle confounders, and air pollution. RESULTS: During follow-up (median = 19.5 y), 11,056 stroke cases were identified. Road traffic noise (Lden) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for individual- and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of <= 2.5 mu m (PM2.5) and NO2]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40-50 vs. <= 40 dB) (HR = 1.12; 95% CI: 0.99, 1.27), but not with higher exposure (>= 50 dB, HR = 0.94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise.
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| 11. |
- Brijs, J., et al.
(författare)
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Humane slaughter of African sharptooth catfish (Clarias gariepinus): Effects of various stunning methods on brain function
- 2021
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Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 531
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors Common slaughter procedures for African sharptooth catfish (Clarias gariepinus) include asphyxiation, ice chilling and exsanguination, which may all cause substantial suffering over prolonged periods of time before death. Therefore, comprehensive evaluations of potentially more humane slaughter procedures for this species are urgently needed. Here, we use a non-invasive electroencephalographic (EEG) method to assess the state of sensibility in African sharptooth catfish in response to various stunning methods (e.g. ice chilling, electrical stunning, electrical stunning followed by exsanguination, percussive stunning, and immersion in isoeugenol). Based on the abolition of visually evoked responses (VERs) on the EEG, ice slurry immersion induced insensibility between 2.6 and 7.6 min, during which catfish exhibited aversive behaviours. Once VERs were lost, they remained absent so long as catfish remained immersed in the ice slurry. Electrical stunning (i.e. exposure to ~1.7 A dm−2 at a water conductivity of ~997 μS cm−1) induced insensibility immediately but not irreversibly. Depending on the duration of the stun (i.e. from 1 to 10 s), catfish either regained VERs immediately or within 4.9 min after the completion of the electrical insult. However, when a 10 s electrical stun was immediately followed by exsanguination and immersion in an ice slurry, the duration of insensibility was sufficient to humanely kill catfish. When administered correctly, manual percussive stunning with a fish priest induced insensibility immediately and irreversibly. However, 36% of catfish regained VERs, which is likely explained by the difficulty associated with administering an accurate manual percussive stun of sufficient force on a live and struggling catfish. Catfish appeared to be sedated following immersion in isoeugenol (i.e. catfish were calm and easy to handle), yet VERs remained present at doses exceeding that recommended for euthanasia in salmonids, which indicates that this substance may not be suitable for stunning catfish. However, the potential for using isoeugenol as a pre-stunning sedative for improving handleability and reducing handling stress of this species warrants further investigation. In conclusion, this study clearly demonstrates that when singularly administered, none of the abovementioned stunning methods could reliably induce insensibility immediately and/or irreversibly without welfare implications. Yet, our findings indicate that these shortcomings can be resolved by using a combination of methods. This could include an electrical or percussive stun to immediately induce insensibility that should be immediately followed by exsanguination and immersion in an ice slurry to maintain insensibility until death.
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| 12. |
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| 13. |
- Martin, Myriam, et al.
(författare)
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Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes.
- 2016
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Ingår i: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 23, s. 903-911
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Tidskriftsartikel (refereegranskat)abstract
- Factor H (FH) binds apoptotic cells to limit the inflammatory potential of complement. Here we report that FH is actively internalized by apoptotic cells to enhance cathepsin L-mediated cleavage of endogenously expressed C3, which results in increased surface opsonization with iC3b. In addition, internalized FH forms complexes with nucleosomes, facilitates their phagocytosis by monocytes and induces an anti-inflammatory biased cytokine profile. A similar cytokine response was noted for apoptotic cells coated with FH, confirming that FH diminishes the immunogenic and inflammatory potential of autoantigens. These findings were supported by in vivo observations from CFH(-/-) MRL-lpr mice, which exhibited higher levels of circulating nucleosomes and necrotic cells than their CFH(+/+) littermates. This unconventional function of FH broadens the established view of apoptotic cell clearance and appears particularly important considering the strong associations with genetic FH alterations and diseases such as systemic lupus erythematosus and age-related macular degeneration.Cell Death and Differentiation advance online publication, 15 January 2016; doi:10.1038/cdd.2015.164.
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| 14. |
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| 15. |
- Yi, Chuixiang, et al.
(författare)
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Climate control of terrestrial carbon exchange across biomes and continents
- 2010
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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| 16. |
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| 17. |
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| 18. |
- Brijs, J., et al.
(författare)
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Bio-sensing technologies in aquaculture: how remote monitoring can bring us closer to our farm animals
- 2021
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Ingår i: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 376:1830
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Tidskriftsartikel (refereegranskat)abstract
- Farmed aquatic animals represent an increasingly important source of food for a growing human population. However, the aquaculture industry faces several challenges with regard to producing a profitable, ethical and environmentally sustainable product, which are exacerbated by the ongoing intensification of operations and increasingly extreme and unpredictable climate conditions. Fortunately, bio-sensors capable of measuring a range of environmental, behavioural and physiological variables (e.g. temperature, dissolved gases, depth, acceleration, ventilation, heart rate, blood flow, glucose and l-lactic acid) represent exciting and innovative tools for assessing the health and welfare of farmed animals in aquaculture. Here, we illustrate how these state-of-the-art technologies can provide unique insights into variables pertaining to the inner workings of the animal to elucidate animal-environment interactions throughout the production cycle, as well as to provide insights on how farmed animals perceive and respond to environmental and anthropogenic perturbations. Using examples based on current challenges (i.e. sub-optimal feeding strategies, sub-optimal animal welfare and environmental changes), we discuss how bio-sensors can contribute towards optimizing the growth, health and welfare of farmed animals under dynamically changing on-farm conditions. While bio-sensors currently represent tools that are primarily used for research, the continuing development and refinement of these technologies may eventually allow farmers to use real-time environmental and physiological data from their stock as 'early warning systems' and/or for refining day-to-day operations to ethically and sustainably optimize production. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.
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| 19. |
- Clulow, Andrew J., et al.
(författare)
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Characterization of Solubilizing Nanoaggregates Present in Different Versions of Simulated Intestinal Fluid
- 2017
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 121:48, s. 10869-10881
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Tidskriftsartikel (refereegranskat)abstract
- The absorption of hydrophobic drugs and nutrients from the intestine is principally determined by the amount that can be dissolved by the endogenous fluids present in the gut. Human intestinal fluids (HIFs) comprise a complex mixture of bile salts, phospholipids, steroids and glycerides that vary in composition in the fed and fasted state and between subjects. A number of simulated intestinal fluid (SIF) compositions have been developed to mimic fasted and fed state intestinal conditions and allow the in vitro determination of drug solubility as a proxy for the maximum dissolved concentration it is possible to reach. In particular these solvents are used during the development of lipophilic and poorly water-soluble drugs but questions remain around the differences that may arise from the source and methods of preparation of these fluids. In this work, a range of SIFs were studied using small angle X-ray scattering (SAXS), cryogenic -transmission electron microscopy (cryo-TEM) and molecular dynamics (MD) simulations in order to analyze their structures. In-house prepared SIFs based on sodium taurodeoxycholate (NaTDC) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) formed oblate ellipsoidal micelles irrespective of lipid concentration and preparation conditions. In contrast, commercially available SIFs based on sodium taurocholate and lecithin formed prolate ellipsoidal micelles in the fed state and vesicles in the fasted state. These structural variations are the likely reason for the dramatic differences sometimes observed in the solubility enhancements for hydrophobic drugs, nutrients and digestion products when using different SIFs. However, the structural homogeneity of the NaTDC/DOPC micelles makes them ideal candidates for standardizing SIF formulations as the structures of the solubilizing nanoaggregates therein are not sensitive to the preparation method.
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| 20. |
- Gräns, Albin, 1979, et al.
(författare)
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A fully implantable multi-channel biotelemetry system for measurement of blood flow and temperature: A first evaluation in the green sturgeon
- 2009
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Ingår i: Hydrobiologia.. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 619:1, s. 11-25
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate a novel fully implantable radio-based blood flow biotelemetry system which allows simultaneously measurement of blood flow on two channels and temperature on one channel, in fish. These are the first recordings of blood flow from free-swimming fish, showing that the system is capable of recording blood flow in the ventral aorta (cardiac output) and celiacomesenteric artery (gastrointestinal blood flow) in green sturgeon Acipenser medirostris exposed to a series of different stimuli for up to 7 days after implantation. The results showed stable base line recordings and blood flow was used to calculated heart rate (f H) and stroke volume (V s). It was possible to reproduce the same type of responses as has previously been reported during exposure to hypoxia, temperature, stress and feeding. The mass of our implant was less than 2% of the body mass which is well within the recommended sizes for surgically implanted telemetry transmitters and it fitted easily within the abdominal cavity of the sturgeon. A fully implantable system minimizes the risk of infection/expulsion and maximizes the likelihood that the studied fish will behave naturally and be treated normally by surrounding fish. The use of biotelemetry in basic comparative physiology and applied animal ecology could help scientists to collect information that has previously been challenging to obtain and to open the possibility for new types of physiological and ecophysiological studies.
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| 21. |
- Gräns, Albin, 1979, et al.
(författare)
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Effects of feeding on thermoregulatory behaviours and gut blood flow in white sturgeon (Acipenser transmontanus) using biotelemetry in combination with standard techniques.
- 2010
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Ingår i: The Journal of experimental biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 213:Pt 18, s. 3198-206
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Tidskriftsartikel (refereegranskat)abstract
- The effects of thermoregulatory behaviours on gut blood flow in white sturgeon Acipenser transmontanus before and after feeding was studied using a blood flow biotelemetry system in combination with a temperature preference chamber. This is the first study to look at cardiovascular responses to feeding in white sturgeon, and also the first time behavioural tests in fish have been combined with recordings of cardiac output, heart rate, cardiac stroke volume and gut blood flow. The results showed strong correlations between gut blood flow and temperature choice after feeding (R(2)=0.88+/-0.03, 6-8 h postprandially and R(2)=0.89+/-0.04, 8-10 h postprandially) but not prior to feeding (R(2)=0.11+/-0.05). Feeding did not affect the actual temperature preference (18.4+/-0.7 degrees C before feeding, 18.1+/-0.7 degrees C, 6-8 h postprandially and 17.5+/-0.5 degrees C, 8-10 h postprandially). Fish instrumented with a blood flow biotelemetry device, and allowed to move freely in the water, had a significantly lower resting heart rate (37.3+/-0.26 beats min(-1)) compared with the control group that was traditionally instrumented with transit-time blood flow probes and kept in a confined area in accordance with the standard procedure (43.2+/-2.1 beats min(-1)). This study shows, for the first time in fish, the correlation between body temperature and gut blood flow during behavioural thermoregulation.
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| 22. |
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| 23. |
- Hjelmstedt, P., et al.
(författare)
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Assessing the effectiveness of percussive and electrical stunning in rainbow trout: Does an epileptic-like seizure imply brain failure?
- 2022
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Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486 .- 1873-5622. ; 552
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Tidskriftsartikel (refereegranskat)abstract
- Both percussive and electrical stunning have been highlighted as methods that can be used to quickly render fish unconscious before being killed. However, accurately assessing unconsciousness in animals following stunning remains challenging, and thus methods for reliable interpretation and validation of different stunning methods are urgently needed. Here, we used a non-invasive technique to continuously record electroencephalograms (EEG) of rainbow trout (Oncorhynchus mykiss) enabling us to compare the effects of both percussive stunning, using a captive bolt gun, and various combinations of electrical stun parameters delivered in water. The EEG signals were assessed for the absence or presence of an epileptic-like seizure and for visually evoked responses (VERs). No epileptic-like seizures or VERs were observed after captive bolt stunning. We found that it is possible to reliably induce an epileptic-like seizure and an immediate, but short lasting, loss of VERs following a 1 s exposure to an electrical field strength of at least 2.8 VRMS cm−1 and current density of 0.22 ARMS dm−2 in water of conductivity of ~1000 μS cm−1 using a 50 Hz AC current. However, to avoid recovery of VERs shortly after the stun, it was necessary to increase the duration of the stun application (≥30 s), the electrical field strength (10.2 VRMS cm−1) and the current density (0.84 ARMS dm−2 respectively). We found no clear relationship between presence and absence of ventilation and VERs following electrical stunning in rainbow trout, highlighting that loss of ventilation may not be a good indicator of brain failure in rainbow trout. Our results clearly show that the presence of an epileptic-like seizure following an electrical stun does not guarantee a prolonged period where the fish is unresponsive to visual stimulation (i.e. absence of VERs). It was further found that VERs can return before the end of the seizure. As both presence of a seizure and absence of VERs have been used independently as indicators of unconsciousness in fish, we emphasize the necessity to carefully consider and evaluate the reliability of neurophysiological indicators of unconsciousness when validating methods to stun fish. © 2022
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| 24. |
- Hjelmstedt, P., et al.
(författare)
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Effects of prophylactic antibiotic-treatment on post-surgical recovery following intraperitoneal bio-logger implantation in rainbow trout
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes. © 2020, The Author(s).
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