| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 3. |
- Pershad, K., et al.
(författare)
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Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display
- 2010
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 23:4, s. 279-288
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Tidskriftsartikel (refereegranskat)abstract
- To demonstrate the utility of phage display in generating highly specific antibodies, affinity selections were conducted on 20 related Src Homology 2 (SH2) domains (ABL1, ABL2, BTK, BCAR3, CRK, FYN, GRB2, GRAP2, LYN, LCK, NCK1, PTPN11 C, PIK3R1 C, PLC gamma 1 C, RASA1 C, SHC1, SH2D1A, SYK N, VAV1 and the tandem domains of ZAP70). The domains were expressed in Escherichia coli, purified and used in affinity selection experiments. In total, 1292/3800 of the resultant antibodies were shown to bind the target antigen. Of the 695 further evaluated in specificity ELISAs against all 20 SH2 domains, 379 antibodies were identified with unique specificity (i.e. monospecific). Sequence analysis revealed that there were at least 150 different clones with 1-19 different antibodies/antigen. This includes antibodies that distinguish between ABL1 and ABL2, despite their 89% sequence identity. Specificity was confirmed for many on protein arrays fabricated with 432 different proteins. Thus, even though the SH2 domains share a common three-dimensional structure and 20-89% identity at the primary structure level, we were able to isolate antibodies with exquisite specificity within this family of structurally related domains.
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| 4. |
- Taussig, Michael J., et al.
(författare)
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ProteomeBinders : planning a European resource of affinity reagents for analysis of the human proteome
- 2007
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 4:1, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- ProteomeBinders is a new European consortium aiming to establish a comprehensive resource of well-characterized affinity reagents, including but not limited to antibodies, for analysis of the human proteome. Given the huge diversity of the proteome, the scale of the project is potentially immense but nevertheless feasible in the context of a pan-European or even worldwide coordination.
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| 5. |
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Advances in Thermal Imaging
- 2021
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Ingår i: Journal of Thermal Biology. - 0306-4565.
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Annan publikation (refereegranskat)abstract
- Thermal imaging, or more correctly infrared thermography, has been widely applied to studies of animal and human biology (see Burnay et al. 1988; McCafferty 2007; Soerensen and Pedersen 2015; Fernandez-Cuevas et al., 2015; Tattersall 2016). This technique provides non-contact measurement of surface temperature, allowing real-time recording of the spatial temperature distribution of a body region, physical structure or habitat of interest. Thermal imaging technology has advanced rapidly in the last decade and is now becoming a key tool in thermal biology. Technological advances include greater spatial and temporal resolution, increased capacity to record and store high resolution radiometric video, as well as reduced device size and portability. In addition, high-quality thermal imaging devices are quickly becoming more affordable, meaning thermal imaging is an increasingly common item of the research tool-kit in many pure and applied fields. The aim of this Special Issue was to highlight how advances in thermal imaging can be used to answer important questions in biology, and to demonstrate how the combination of this technology with novel analytical methods can further advance our conceptual understanding of thermal biology.
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| 6. |
- McCafferty, Dominic J., et al.
(författare)
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Editorial : Advances in thermal imaging
- 2021
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Ingår i: Journal of Thermal Biology. - : Elsevier BV. - 0306-4565. ; 102
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Nord, Andreas, et al.
(författare)
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Avian red blood cell mitochondria produce more heat in winter than in autumn
- 2021
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Ingår i: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 1530-6860. ; 35:5
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Tidskriftsartikel (refereegranskat)abstract
- Endotherms in cold regions improve heat-producing capacity when preparing for winter. We know comparatively little about how this change is fueled by seasonal adaptation in cellular respiration. Thus, we studied the changes of mitochondrial function in red blood cells in sympatric Coal (Periparus ater), Blue (Cyanistes caeruleus), and Great (Parus major) tits between autumn and winter. These species differ more than twofold in body mass and in several aspects of their foraging ecology and social dominance, which could require differential seasonal adaptation of energy expenditure. Coal and Great tits in particular upregulated the mitochondrial respiration rate and mitochondrial volume in winter. This was not directed toward ATP synthesis, instead reflecting increased uncoupling of electron transport from ATP production. Because uncoupling is exothermic, this increased heat-producing capacity at the sub-cellular level in winter. This previously unexplored the route of thermogenesis in birds should be addressed in future work.
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| 8. |
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| 9. |
- Asherson, PJ, et al.
(författare)
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Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study
- 2023
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 222:1, s. 7-17
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Tidskriftsartikel (refereegranskat)abstract
- Research has shown that 20–30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.AimsTo estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.MethodWe conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16–25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.ResultsIn the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI −2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.ConclusionsADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.
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| 10. |
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| 11. |
- Karlsson, Niklas, 1967, et al.
(författare)
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The economics of meaning
- 2004
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Ingår i: Nordic Journal of Political Economy. ; :30, s. 61-75
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we draw attention to an important motive the desire for meaning that drive considerable human behavior and economic activity, but has been largely ignored by economists. We distinguish four interpretations of meaning that differ in the degree to which they are amenable to modeling using the standard economic tools of utility maximization. These four interpretations are, in decreasing order of their amenability to modeling in conventional terms: (1) meaning as a resolution of preferences; (2), meaning as an extension of oneself either socially or temporally; (3) meaning as an act of making sense of ones life; and (4) meaning as an assertion of free will. Drawing upon psychology and literature we analyze implications of these four interpretations of meaning for economics.
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| 12. |
- McCafferty, Dominic J., et al.
(författare)
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Challenges of measuring body temperatures of free-ranging birds and mammals
- 2015
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Ingår i: Animal Biotelemetry. - : Springer Science and Business Media LLC. - 2050-3385. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The thermal physiology of most birds and mammals is characterised by considerable spatial and temporal variation in body temperature. Body temperature is, therefore, a key parameter in physiological, behavioural and ecological research. Temperature measurements on freely moving or free-ranging animals in the wild are challenging but can be undertaken using a range of techniques. Internal temperature may be sampled using thermometry, surgically implanted loggers or transmitters, gastrointestinal or non-surgically placed devices. Less invasive approaches measure peripheral temperature with subcutaneous passive integrated transponder tags or skin surface-mounted radio transmitters and data loggers, or use infrared thermography to record surface temperature. Choice of technique is determined by focal research question and region of interest that reflects appropriate physiological or behavioural causal mechanisms of temperature change, as well as welfare and logistical considerations. Particularly required are further studies that provide opportunities of continuously sampling from multiple sites from within the body. This will increase our understanding of thermoregulation and temperature variation in different parts of the body and how these temperatures may change in response to physiological, behavioural and environmental parameters. Technological advances that continue to reduce the size and remote sensing capability of temperature recorders will greatly benefit field research.
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| 13. |
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| 14. |
- Nord, Andreas, et al.
(författare)
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Evaluation of two methods for minimally invasive peripheral body temperature measurement in birds
- 2016
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Ingår i: Journal of Avian Biology. - : Wiley. - 0908-8857. ; 47:3, s. 417-417
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Tidskriftsartikel (refereegranskat)abstract
- Body temperature (Tb) is a valuable parameter when assessing the physiological state of animals, but its widespread measurement is often constrained by methods that are invasive or require frequent recapture of animals. Alternatives based on automated remote sensing of peripheral Tb show promise, but little is known about their strengths and limitations. We measured peripheral Tb in great tits Parus major with subcutaneously implanted passive integrated transponders (PIT tags) and externally attached radio transmitters to determine repeatability of measurements, sensitivity of each method to variation in ambient temperature (Ta) and wind speed, the relationship between methods, and their ability to capture circadian variation in Tb. Repeatability of measurements by radio transmitters was high (> 80%) when readings were taken within 20 min, but reduced to 16% when measures were spaced 3.5 h apart. PIT tag data for the 3.5 h interval were more repeatable (33%) and less variable (cv). Data were affected by Ta with a stronger effect on the externally attached transmitters, but the influence of wind speed was small for both methods. There was a significant positive relationship between transmitter- and PIT tag temperature during both days and nights. Both methods were equally suited to detect diel changes in peripheral Tb. However, transmitters offered longer detection distance and better temporal resolution. These qualities should be considered when deciding how to collect Tb data remotely. If properly deployed, both methods allow measurement of peripheral Tb over a wide range of natural systems and conditions in small, free-ranging, birds.
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| 15. |
- Page, Jennifer L., et al.
(författare)
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Experimental warming during incubation improves cold tolerance of blue tit (Cyanistes caeruleus) chicks
- 2022
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 225:10
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and increasing air temperature may alter environmental conditions for developing birds, with a range of phenotypic consequences for offspring. The thermal environment during incubation may affect the trade-off between growth and thermoregulation, but the effects of temperature on the ontogeny of endothermy are not fully understood. Therefore, we experimentally tested whether heating the nest cup of Eurasian blue tits (Cyanistes caeruleus) during incubation would influence cold tolerance of the chicks after hatching. Chicks from both heated and control nests showed a decrease in cooling rate with age as they became increasingly endothermic and homeothermic. However, chicks from previously heated nests cooled at a lower rate per unit surface area and from across the whole body. These chicks also had a greater body mass during the first 12 days of life compared with chicks from control nests. Lower cooling rates in heated chicks may reflect greater thermogenic capacity or a reduced surface area to volume ratio owing to a greater body mass. Future projections for climate change predict rising air temperature and increased likelihood of heatwaves, even in temperate regions. Our results indicate that nest microclimate can affect thermoregulation in offspring, and thus may be used to predict some of the future physiological responses of birds to climate change during breeding.
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| 16. |
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| 17. |
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| 18. |
- Stone, David W., et al.
(författare)
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Plumage development and environmental factors influence surface temperature gradients and heat loss in wandering albatross chicks
- 2021
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Ingår i: Journal of Thermal Biology. - : Elsevier BV. - 0306-4565. ; 97
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Tidskriftsartikel (refereegranskat)abstract
- Young birds in cold environments face a range of age-specific thermal challenges. Studying the thermal biology of young birds throughout ontogeny may further our understanding of how such challenges are met. We investigated how age and environmental parameters influenced surface temperature gradients across various body regions of wandering albatross (Diomedea exulans) chicks on Bird Island, South Georgia. This study was carried out over a 200 d period during the austral winter, from the end of the brood-guard period until fledging, bridging a gap in knowledge of surface temperature variation and heat loss in developing birds with a long nestling stage in severe climatic conditions. We found that variation in surface temperature gradients (i.e. the difference between surface and environmental temperature) was strongly influenced by chick age effects for insulated body regions (trunk), with an increase in the surface temperature gradient that followed the progression of plumage development, from the second set of down (mesoptiles), to final chick feathers (teleoptiles). Environmental conditions (primarily wind speed and relative humidity) had a stronger influence on the gradients in uninsulated areas (eye, bill) than insulated regions, which we interpret as a reflection of the relative degree of homeothermy exhibited by chicks of a given age. Based on biophysical modelling, total heat loss of chicks was estimated to increase linearly with age. However, mass specific heat loss decreased during the early stages of growth and then subsequently increased. This was attributed to age-related changes in feather growth and activity that increased surface temperature and, hence, metabolic heat loss. These results provide a foundation for further work on the effects of environmental stressors on developing chicks, which are key to understanding the physiological responses of animals to changes in climate in polar regions.
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| 19. |
- Strauß, Aurelia F.T., et al.
(författare)
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Using skin temperature and activity profiles to assign chronotype in birds
- 2022
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Ingår i: Animal Biotelemetry. - : Springer Science and Business Media LLC. - 2050-3385. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronotypes describe consistent differences between individuals in biological time-keeping. They have been linked both with underlying variation in the circadian system and fitness. Quantification of chronotypes is usually by time of onset, midpoint, or offset of a rhythmic behaviour or physiological process. However, diel activity patterns respond flexibly to many short-term environmental influences, which can make chronotypes hard to identify. In contrast, rhythmic patterns in physiological processes, such as body temperature, may provide more robust insights into the circadian basis of chronotypes. These can be telemetrically recorded from skin-mounted, temperature-sensitive transmitters, offering minimally invasive opportunities for working on free-ranging animals in the wild. Currently, computational methods for deriving chronotype from skin temperature require further development, as time series are often noisy and incomplete. Here, we investigate such methods using simultaneous radio telemetry recordings of activity and skin temperature in a wild songbird model (Great Tit Parus major) temporarily kept in outdoor aviaries. Our aims were to first develop standardised selection criteria to filter noisy time series of skin temperature and activity, to second assign chronotype based on the filtered recordings, and to third compare chronotype as assigned based on each of the two rhythms. After the selection of rhythmic data using periodicity and autocorrelation parameters, chronotype estimates (onset and offset) were extracted using four different changepoint approaches for skin temperature and one approach for activity records. The estimates based on skin temperature varied between different approaches but were correlated to each other (onset: correlation coefficient r = 0.099–0.841, offset: r = 0.131–0.906). In contrast, chronotype estimates from skin temperature were more weakly correlated to those from activity (onset: r = −0.131–0.612, offset: r = −0.040– −0.681). Overall, chronotype estimates were less variable and timed later in the day for activity than for skin temperature. The distinctions between physiological and behavioural chronotypes in this study might reflect differences in underlying mechanisms and in responsiveness to external and internal cues. Thus, studying each of these rhythms has specific strengths, while parallel studies of both could inform broadly on natural variation in biological time-keeping, and may allow assessment of how biological rhythms relate to changes in the environment.
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| 20. |
- Winder, Lucy, et al.
(författare)
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Body surface temperature responses to food restriction in wild and captive great tits
- 2020
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 223:8
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Tidskriftsartikel (refereegranskat)abstract
- During winter at temperate and high latitudes, the low ambient temperatures, limited food supplies and short foraging periods mean small passerines show behavioural, morphological and physiological adaptations to reduce the risk of facing energy shortages. Peripheral tissues vasoconstrict in low ambient temperatures to reduce heat loss and cold injury. Peripheral vasoconstriction has been observed with food restriction in captivity but has yet to be explored in free-ranging animals. We experimentally food restricted both wild and captive great tits (Parus major) during winter months and measured surface temperatures of the bill and eye region using thermal imaging, to investigate whether birds show rapid local heterothermic responses, which may reduce their thermoregulatory costs when facing a perceived imminent food shortage. Our results of a continuously filmed wild population showed that bill temperature was immediately reduced in response to food restriction compared with when food was available ad libitum, an apparent autonomic response. Such immediacy implies a ‘pre-emptive’ response before the bird experiences any shortfalls in energy reserves. We also demonstrate temporal variation in vasoconstriction of the bill, with bill temperature gradually rising throughout the food restriction after the initial drop. Eye-region temperature in the wild birds remained at similar levels throughout food restriction compared with unrestricted birds, possibly reflecting the need to maintain steady circulation to the central nervous and visual systems. Our findings provide evidence that birds selectively allow the bill to cool when a predictable food supply is suddenly disrupted, probably as a means of minimising depletion of body reserves for a perceived future shortage in energy.
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