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| 2. |
- Andersen, Caroline, et al.
(författare)
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Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 252-258
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from SkAyenne (n = 272) and Vasterbotten (n = 100). Age- and sex-matched patients with type 2 diabetes were included as controls. Data on the use of oral hypoglycaemic agents (OHAs), insulin and insulin-OHA combination therapy was retrieved from the medical records. Poor glycaemic control was defined as HbA(1c) a parts per thousand yen7.0% (a parts per thousand yen53 mmol/mol) at follow-up. The individuals with LADA and with type 2 diabetes were followed for an average of 107 months. LADA patients were leaner than type 2 diabetes patients at diagnosis (BMI 27.7 vs 31.0 kg/m(2); p < 0.001) and follow-up (BMI 27.9 vs 30.2 kg/m(2); p < 0.001). Patients with LADA had been treated with insulin for longer than those with type 2 diabetes (53.3 vs 28.8 months; p < 0.001). There was no significant difference between the patient groups with regard to poor glycaemic control at diagnosis, but more patients with LADA (67.8%) than type 2 diabetes patients (53.0%; p < 0.001) had poor glycaemic control at follow-up. Patients with LADA had worse glycaemic control at follow-up compared with participants with type 2 diabetes (OR = 1.8, 95% CI 1.2, 2.7), adjusted for age at diagnosis, HbA(1c), BMI at diagnosis, follow-up time and duration of insulin treatment. Individuals with LADA have worse glycaemic control than patients with type 2 diabetes despite a longer time on insulin therapy.
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| 4. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 5. |
- Granio, Ophélia, et al.
(författare)
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Adenovirus 5-fiber 35 chimeric vector mediates efficient apical correction of the CFTR defect in cystic fibrosis primary airway epithelia.
- 2010
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Ingår i: Human gene therapy. - : Mary Ann Liebert Inc. - 1557-7422 .- 1043-0342. ; 21:3, s. 251-269
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Tidskriftsartikel (refereegranskat)abstract
- In vivo gene transfer to the human respiratory tract using Adenovirus serotype 5 (Ad5) vectors has revealed their limitations related to inefficient gene transfer, host antiviral response and innate adenoviral toxicity. In the present work, we compared the cytotoxicity and efficiency of Ad5 and a chimeric Ad5F35 vector with respect to CFTR gene transfer to cystic fibrosis (CF) and non-CF human airway epithelial cells. We found that high doses of Ad5 vector had an adverse effect on the function of exogenous and endogenous CFTR. Results obtained with Ad5 capsid mutants suggested that the RGD motifs on the penton base capsomers were responsible for the negative effect on the CFTR function. This negative interference was not a result of a lower level of biosynthesis and/or altered cellular trafficking of the CFTR protein, but rather from an indirect mechanism of functional blockage of CFTR, related to the RGD-integrin-mediated endocytic pathway of Ad5. No negative interference with CFTR was observed for Ad5F35, an Ad5-based vector pseudotyped with fibers from Ad35, a serotype which uses another cell entry pathway. In vitro, Ad5F35 vector expressing the GFP-tagged CFTR (Ad5F35-GFP-CFTR) showed a 30-fold higher efficiency of transduction and chloride channel correction in CFTR-deficient cells, compared to Ad5GFP-CFTR. Ex vivo, Ad5F35-GFP-CFTR had the capacity to transduce efficiently reconstituted airway epithelia from CF patients (CF-HAE) via the apical surface, restored the chloride channel function at relatively low vector doses, and showed a relatively stable expression of GFP-CFTR for several weeks.
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| 7. |
- Lees, John J., 1986-, et al.
(författare)
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The physiological and neuroendocrine correlates of hunger in the Red Junglefowl (Gallus gallus)
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The ability to regulate food intake is critical to survival. The hypothalamus is central to this regulation, integrating peripheral signals of energy availability. Although our understanding of hunger in rodents is advanced, an equivalent understanding in birds is lacking. In particular, the relationship between peripheral energy indices and hypothalamic ‘hunger’ peptides, agouti-related protein (AgRP), pro- opiomelanocortin (POMC) and neuropeptide Y (NPY) is poorly understood. Here, we compare AgRP, POMC and NPY RNA levels in the hypothalamus of Red Junglefowl chicks raised under ad libitum, chronic restriction and intermittent feeding regimens. Hypothalamic gene expression differed between chronically and intermittently restricted birds, confirming that different restriction regimens elicit different patterns of hunger. By assessing the relationship between hypothalamic gene expression and carcass traits, we show for the first time in birds that AgRP and POMC are responsive to fat-related measures and therefore represent long-term energy status. Chronically restricted birds, having lower indices of fat, show elevated hunger according to AgRP and POMC. NPY was elevated in intermittently fasted birds during fasting, suggesting a role as a short-term index of hunger. The different physiological and neuroendocrine responses to quantitative versus temporal feed restriction provide novel insights into the divergent roles of avian hunger neuropeptides.
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| 8. |
- Lindholm, Caroline, et al.
(författare)
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Growth heterogeneity in broiler breeder pullets is settled before the onset of feed restriction but is not predicted by size at hatch
- 2017
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Ingår i: Journal of Animal Science. - Champaign, IL, United States : American Society of Animal Science. - 0021-8812 .- 1525-3163. ; 95:1, s. 182-193
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Tidskriftsartikel (refereegranskat)abstract
- Uniform growth is a desirable trait in all large-scale animal production systems because it simplifies animal management and increases profitability. In parental broiler flocks, so-called broiler breeders, low growth uniformity is largely attributed to the feed competition that arises from quantitatively restricted feeding. As feed restriction is crucial to maintaining healthy and fertile breeders, several practices for reducing feed competition and the associated growth heterogeneity have been suggested and range from nutrient dilution by increasing fiber content in feed to intermittent fasting with increased portion size (“skip a day”), but no practice appears to be entirely effective. The fact that a large part of the heterogeneity remains even when feed competition is minimized suggests that some growth variation is caused by other factors. We investigated whether this variation arises during embryonic development (as measured by size at hatch) or during posthatch development by following the growth and body composition of birds of varying hatch sizes. Our results support the posthatch alternative, with animals that later grow to be small or large (here defined as >1 SD lighter or heavier than mean BW of the flock) being significantly different in size as early as 1 d after gaining access to feed (P < 0.05). We then investigated 2 possible causes for different postnatal growth: that high growth performance is linked 1) to interindividual variations in metabolism (as measured by cloacal temperature and verified by respirometry) or 2) to higher levels of social motivation (as measured in a social reinstatement T-maze), which should reduce the stress of being reared in large-scale commercial flocks. Neither of these follow-up hypotheses could account for the observed heterogeneity in growth. We suggest that the basis of growth heterogeneity in broiler breeder pullets may already be determined at the time of hatch in the form of qualitatively different maternal investments or immediately thereafter as an indirect result of differences in incubation conditions, hatching time, and resulting fasting time. Although this potential difference in maternal investment is not seen in body mass, tarsometatarsal length, or full body length of day-old chicks arriving at the farm, it may influence the development of differential feed and water intake during the first day of feeding, which in turn has direct effects on growth heterogeneity.
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| 9. |
- Lindholm, Caroline, et al.
(författare)
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Higher fear of predators does not decrease outdoor range use in free-range Rowan Ranger broiler chickens
- 2016
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Ingår i: Acta agriculturae Scandinavica. Section A, Animal science. - : TAYLOR & FRANCIS AS. - 0906-4702 .- 1651-1972. ; 66:4, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- Organic chicken production is currently experiencing a boom in Sweden, but has only recently gained access to a commercial slow-growing broiler strain, the Rowan Ranger. While these chickens are reported to grow at rates better suited to organic production than previously available strains, anecdotal evidence suggested increased fearfulness in this strain and concerns were raised that this may deter the birds from accessing the range. We subjected Rowan Rangers and fast-growing Ross 308 raised on the same organic farm to a set of behavioural tests while also tracking activity and outdoor use. The results suggest that although Rowan Rangers indeed show longer durations of tonic immobility, an index of predator-related fear, both strains made an outdoor visit on average once every 1.5 h and typically spent around 5% of their days in the range. Overall however, our results support the transition to Rowan Rangers in organic chicken production in Sweden.
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| 10. |
- Lindholm, Caroline, 1984-
(författare)
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Intermittent fasting in chickens : Physiological mechanisms and welfare implications for broiler breeders
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Broiler breeder chickens are the parent stock used to produce broiler chickens raised for human consumption and have long been caught in a welfare dilemma. The immensely successful selection of fast-growing meat-type chickens over the last 80 years has created a remarkably efficient meat-producer and given us access to cheap chicken meat but has also created health problems for the animals. These problems especially affect the breeder generation, which must be raised with strict feed restriction to limit weight gain and thus maintain physical health and normal fertility. At the same time, however, feed restriction causes chronic hunger and feeding frustration with reduced animal welfare as a result. In the EU alone 60 million breeders are affected annually and although the problem is well-known within the industry, there is financial incentive to keep selecting for even higher growth potential in broilers, further increasing the problems for broiler breeders.Many strategies for reducing the impact of growth restriction on breeder welfare have been suggested and are usually aimed at somehow increasing the amount of feed given at feeding times. This can be done either through adding bulky fibers to the diet or by reducing feeding frequency. In this thesis, focus is on the latter as we explore the effects of intermittent fasting (IF) on the welfare of young broiler breeders as well as wild-type Red Junglefowl. Intermittent fasting, or “skip-a-day” feeding, is supposedly the most common feeding strategy for broiler breeders worldwide but is perceived as welfare-reducing and thus illegal in Sweden and several other European countries. In spite of this, the scientific knowledge of how this type of feeding affects chicken welfare is scarce.Assessing the overall effect of IF on breeder welfare is complicated by large variations in both physiological and behavioral parameters between feeding and fasting days, but it does appear that chicken welfare is improved at least on the feeding days of IF regimens. It also seems that some of the health benefits reported from mammalian studies of IF may apply to chickens as well, although behavioral indicators still point to welfare issues unless the level of feed restriction can be relaxed. In comparison with daily feed restriction, IF appears to increase the motivation for feed consumption but to reduce the motivation for appetitive behaviors such as foraging, which may explain why birds fed on this type of schedule are often reported as calmer.
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