| 1. |
- Lindhe Norberg, Ulla, et al.
(författare)
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Evolutionary divergence of body size and wing and leg structure in relation to foraging mode in Darwin's Galapagos finches
- 2023
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Ingår i: Biological Journal of the Linnean Society. - 0024-4066. ; 140:2, s. 240-60
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Tidskriftsartikel (refereegranskat)abstract
- The wings, legs, and tail in Darwin's finches show many clear adaptations to different types of locomotion used during foraging. We use size scaling to analyse how various characters vary with body mass to clarify dimensional relationships. The selective advantage of a character is judged in terms of energy savings. The wing aspect ratio (4.6-4.9) is very low, so the energy costs for flight are high. Low body mass, low wing loading, and short arm wings in the warbler finch, small tree finch, and small ground finch promote agility and manoeuvrability among vegetation, along with short wings in the warbler finch. Evolution towards a shorter arm wing seems to be favoured in the smaller finch species. Long legs, long toes, and long curved claws are adaptations for climbing/clinging locomotion without tail support (woodpecker finch, small and large tree finches, cactus finch but having short legs). Selection for longer legs seems to act towards a lengthening of the tarsometatarsus. The climbing technique in the woodpecker finch is described. We discuss how the diversification in the beaks relates to the locomotion organs.
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| 2. |
- Lindhe Norberg, Ulla, et al.
(författare)
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Scaling of wingbeat frequency with body mass in bats and limits to maximum bat size
- 2012
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 215, s. 711-722
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Tidskriftsartikel (refereegranskat)abstract
- The ability to fly opens up ecological opportunities but flight mechanics and muscle energetics impose constraints, one of which is that the maximum body size must be kept below a rather low limit. The muscle power available for flight increases in proportion to flight muscle mass and wingbeat frequency. The maximum wingbeat frequency attainable among increasingly large animals decreases faster than the minimum frequency required, so eventually they coincide, thereby defining the maximum body mass at which the available power just matches up to the power required for sustained aerobic flight. Here, we report new wingbeat frequency data for 27 morphologically diverse bat species representing nine families, and additional data from the literature for another 38 species, together spanning a range from 2.0 to 870.g. For these species, wingbeat frequency decreases with increasing body mass as M b-0.26. We filmed 25 of our 27 species in free flight outdoors, and for these the wingbeat frequency varies as M b-0.30 These exponents are strikingly similar to the body mass dependency M b-0.27. among birds, but the wingbeat frequency is higher in birds than in bats for any given body mass. The downstroke muscle mass is also a larger proportion of the body mass in birds. We applied these empirically based scaling functions for wingbeat frequency in bats to biomechanical theories about how the power required for flight and the power available converge as animal size increases. To this end we estimated the muscle massspecific power required for the largest flying extant bird (12-16.kg) and assumed that the largest potential bat would exert similar muscle mass-specific power. Given the observed scaling of wingbeat frequency and the proportion of the body mass that is made up by flight muscles in birds and bats, we estimated the maximum potential body mass for bats to be 1.1-2.3.kg. The largest bats, extinct or extant, weigh 1.6.kg. This is within the range expected if it is the bat characteristic flight muscle mass and wingbeat frequency that limit the maximum body mass in bats. It is only a tenth the mass of the largest flying extant bird. © 2012. Published by The Company of Biologists Ltd.
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| 3. |
- Andersson, Malte, 1941, et al.
(författare)
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”Minskande befolkning är inte problemet”
- 2020
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Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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| 4. |
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| 5. |
- Barri, Thaer, et al.
(författare)
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Extracting Syringe for determination of organochlorine pesticides in leachate water and soil-water slurry: A novel technology for environmental analysis
- 2006
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1111:1, s. 11-20
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Tidskriftsartikel (refereegranskat)abstract
- The Extracting Syringe (ESy), a novel membrane-based sample preparation technique directly coupled as an autosampler to gas chromatography, has been employed for the analysis of organochlorine pesticides (OCPs) in raw leachate water. The ESy has also been applied for extraction of OCPs from contaminated soil samples and its performance has been compared to liquid-solid extraction (LSE) and accelerated solvent extraction (ASE). Extraction of 3-mL leachate sample at the optimised conditions resulted in enrichment factors from 32 (Endrin aldehyde) to 242 (Endrin) and detection limits from 1 to 20 ng/L. The inter-day and intra-day repeatability (% RSD) at 100 and 500 ng/L were < 6% and < 24%, respectively. The relative recovery at 100 and 500 ng/L ranged from 68% (Aldrin) to 116% (Endrin aldehyde); except Heptachlor that showed 51 and 60%, respectively. The ESy extraction of the slurry-made soil samples revealed occurrence of Endosulfan I (18.2 mu g/g soil), 4,4'-DDE (2.6 ng/g soil), Endosulfan 11 (8.7 mu g/g soil) and Endosulfan sulfate (1.1 mu g/g soil); showing good agreement with LSE results. The total ESy consumption of organic solvents was 4.2 mL from which only 0.6 mL n-undecane was used during the extraction step (7 mu L for the extraction per se), while in the LSE and ASE, it was 420 and 18.1 mL, respectively. The ESy extraction time (0.5 h) was comparable to the ASE time (0.6 h); and the time required for the LSE was 3.75 h. To sum up, the ESy has shown its competency to LSE and ASE technologies, demonstrating its applicability for environmental analysis of organic pollutants, towards green techniques for green environment. (c) 2006 Elsevier B.V. All rights reserved.
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| 6. |
- Barri, Thaer, et al.
(författare)
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Miniaturized and automated sample pretreatment for determination of PCBs in environmental aqueous samples using an on-line microporous membrane liquid-liquid extraction-gas chromatography system
- 2004
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 76:7, s. 1928-1934
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Tidskriftsartikel (refereegranskat)abstract
- A new, fast, and automated sample pretreatment technique for determination of lipophilic organic compounds in aqueous samples has been developed and applied to the determination of polychlorinated biphenyls (PCBs) in environmental river water. It is based on miniaturized microporous membrane liquid-liquid extraction coupled on-line to gas chromatography (GC) with electron capture detection. The heart of the system that simultaneously connects the sample pretreatment step to the final GC analysis has been named the extracting syringe (ESy). The ESy carries a miniaturized membrane extraction card attached to an electrically and mechanically designed installment and is mounted directly over a GC injector for fully automated injection of the extract. A method was developed to extract 10 PCB congeners from 1-mL water samples (after addition of 40% acetonitrile) with an extraction time of 10 min. The optimized methodology showed good linearity (in the dynamic concentration range of 5 ng L-1-1 mug L-1), enrichment factors of 33-40 times, repeatable extractions (RSD 2-5%, n = 4), a
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| 7. |
- Barthelsson, Cajsa, et al.
(författare)
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Sense of coherence and other predictors or pain and health following laparoscopic cholecystectomy
- 2011
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Ingår i: Scandinavian Journal of Caring Sciences. - Malden, MA : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 25:1, s. 143-150
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Tidskriftsartikel (refereegranskat)abstract
- Pain is the most common symptom following laparoscopic cholecystectomy (LC) and might delay discharge from hospital after day surgery. A patient’s ability to manage stressful situations can be assessed by the sense of coherence (SOC) and has been proposed to predict health. The aim of this study was to investigate predictors of average pain the first postoperative week after LC, and predictors of changes in perceived health, with special reference to individual coping resources measured by the Sense of Coherence Scale. Furthermore, a test–re-test was performed on SOC to evaluate the stability in the context of LC surgery. Method: Seventy-three patients completed questionnaires about SOC, health status, pain, anxiety, symptom occurrence and symptom distress preoperatively, postoperative day 1–7 and after 1 and 6 months following LC. Results: By multiple regression, 23% of the variability in pain intensity could be explained by the variables age, SOC and education. Age was the strongest predictor. Further, 19% of the change in health between day 7 and 1 month could be explained by the two variables symptom distress the first postoperative day and SOC. The test–re-test of SOC had a correlation coefficient (r) of 0.55. Forty-six patients (63%) remained within ± 10% of their preoperative SOC score at 6 months, 11 patients (15%) decreased and 16 patients (22%) increased their SOC values. Conclusion: SOC was found to be a significant but weak predictor of pain intensity the first week after LC. Furthermore, patients scoring low SOC values experienced a delay in their health improvement. SOC was more unstable over time than previously suggested. Further, interventional studies are needed to clarify if SOC might be a clinically useful measure to identify vulnerable patients undergoing LC surgery.
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| 8. |
- Bergström, Staffan, et al.
(författare)
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Extracting syringe for extraction of phthalate esters in aqueous environmental samples
- 2007
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 1873-4324 .- 0003-2670. ; 594:2, s. 240-247
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Tidskriftsartikel (refereegranskat)abstract
- The use of the extracting syringe (ESy), a fully automated membrane-based extraction technique, for analysis of phthalate esters in complex aqueous samples has been investigated. The ESy, working as an autosampler that combines the extraction process and injection into the gas chromatograph (GC) in one single step, is placed on top of the GC equipped with a flame ionisation detector. The aqueous samples are loaded in a tray and automatically extracted by employing microporous membrane liquid-liquid extraction principle. After the extraction, the extract is directly injected into the GC's programmable temperature vaporisation injector. Six different phthalate esters were used as model compounds. Four extraction solvents were tested and the addition of sample organic modifier was examined. Toluene was the optimal solvent to use for extraction. Due to the large variation in polarity of phthalate esters, 50% methanol as organic modifier had to be added to the samples so as to extract the most nonpolar phthalate esters; di-2-ethylhexylphthalate and di-n-octylphthalate, whereas the other four relatively polar phthalate esters were extracted from unmodified samples. No significant difference between extraction of river water, leachate water from a landfill and reagent water was noted, except for minor deviations. The extraction time was 20 min for extraction of a 1-mL sample, resulting in a good linearity for all aqueous media investigated, good enrichment factors (54-110 folds) and low LOD values (0.2-10 ng mL(-1)) and relative standard deviation (%R.S.D.; 0.9-3.7%).
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| 9. |
- Björnsson, Marcus A, et al.
(författare)
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A Recirculatory Model for Pharmacokinetics and the Effects on Bispectral Index After Intravenous Infusion of the Sedative and Anesthetic AZD3043 in Healthy Volunteers
- 2015
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Ingår i: Anesthesia and Analgesia. - 0003-2999 .- 1526-7598. ; 121:4, s. 904-913
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers.METHODS: Arterial and venous plasma concentrations of AZD3043 and BIS were measured in 2 clinical studies in 125 healthy volunteers, where AZD3043 was given as a 1-minute bolus (1-6 mg/kg), a 30-minute infusion (1-81 mg/kg/h), or 0.8 + 10, 1 + 15, 3 + 30, and 4 + 40 (mg/kg bolus + mg/kg/h infusion for 30 minutes). Population PK/pharmacodynamic analysis was performed with NONMEM.RESULTS: A recirculatory model, comprising a series of 5 compartments for the transit of drug between venous and arterial plasma, 2 peripheral distribution compartments, and 1 compartment for the nondistributive transit of drug from arterial to venous plasma, described the PK of AZD3043. Systemic clearance was high (2.2 L/min; 95% confidence interval, 2.12-2.25), and apparent volumes of distribution were low, leading to a short elimination half-life. The apparent volumes of distribution of the arterial and peripheral compartments increased with increasing administered dose, giving a total apparent volume of distribution of 15 L after the lowest dose and 37 L after the greatest dose. A sigmoid maximum effect (Emax) model with an EC50 of 15.6 µg/mL and a γ of 1.7 described the relationship between AZD3043 effect-site concentrations and BIS. The between-subject variability in EC50 was 37%. An effect compartment model, with a half-life of the equilibration rate constant ke0 of 1.1 min, described the delay in effect in relation to the arterial plasma concentrations.CONCLUSIONS: AZD3043 had a high clearance and a low apparent volume of distribution, leading to a short half-life. However, the apparent volume of distribution was dose dependent (P < 0.001), leading to an increased half-life with increasing dose. The distribution to the effect site was fast and together with the short plasma half-life led to a fast onset and offset of effects.
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| 10. |
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| 11. |
- Jönsson, Håkan, et al.
(författare)
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Minimera mängden producerat avfall
- 2003
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Ingår i: Miljömagasinet. ; 2003-02-21, s. 4-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Liljeqvist, Jan-Åke, 1954, et al.
(författare)
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Asymptomatically shed recombinant herpes simplex virus type 1 strains detected in saliva
- 2009
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:Pt 3, s. 559-66
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen infecting most individuals worldwide. The majority of HSV-1-infected individuals have no clinical symptoms but shed HSV-1 asymptomatically in saliva. Recent phylogenetic analyses of HSV-1 have defined three genetic clades (A-C) and recombinants thereof. These data have all been based on clinical HSV-1 isolates and do not cover genetic variation of asymptomatically shed HSV-1. The primary goal of this study was to investigate such variation. A total of 648 consecutive saliva samples from five HSV-1-infected volunteers was collected. Asymptomatic shedding was detected on 7.6 % of the days from four subjects. The HSV-1 genome loads were quantified with real-time PCR and varied from 1x10(2) to 2.8x10(6) copies of virus DNA (ml saliva)(-1). Phylogenetic network analyses and bootscanning were performed on asymptomatically shed HSV-1. The analyses were based on DNA sequencing of the glycoprotein I gene, and also of the glycoprotein E gene for putative recombinants. For two individuals with clinical HSV-1 infection, the same HSV-1 strain was shed asymptomatically as induced clinical lesions, and sequence analyses revealed that these strains clustered distinctly to clades A and B, respectively. For one of the subjects with no clinical HSV-1 infection, a recombinant strain was identified. The other truly asymptomatic individual shed evolutionarily distinct HSV-1 strains on two occasions. The first strain was classified as a recombinant and the other strain clustered in clade A. High replication rates of different strains in the same person may facilitate the creation of recombinant clinical HSV-1 strains.
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| 13. |
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| 14. |
- Norberg, J, et al.
(författare)
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Supported liquid membrane extraction of urinary trans, trans-muconic acid, a biomarker for benzene exposure
- 2002
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Ingår i: Journal of Separation Science. - 1615-9314. ; 25:5-6, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- In this study, sample preparation of urinary trans, trans-muconic acid (tt-MA), a minor metabolite and biomarker of benzene, by means of Supported Liquid Membrane (SLM) extraction has been investigated. The sample extract was automatically transferred on-line to an ion exchange chromatographic column and the analytes were detected using a photodiode array detector. Automation of the system was accomplished using a robotic sample preparation processor integrated into the chromatographic system. Detection limits calculated from the baseline noise was in the sub-ppb range, and quantification of tt-MA is safe down to 10 ppb.
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| 15. |
- Norberg, Peter, 1974, et al.
(författare)
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A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.
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| 16. |
- Norberg, Peter, 1974, et al.
(författare)
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Complete-genome phylogenetic approach to varicella-zoster virus evolution: genetic divergence and evidence for recombination.
- 2006
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Ingår i: Journal of virology. - 0022-538X. ; 80:19, s. 9569-76
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving large numbers of globally distributed clinical isolates, suggest that this virus has diverged into at least three distinct genotypes designated European (E), Japanese (J), and mosaic (M). In the present study, we determined and analyzed the complete genomic sequences of two M VZV strains and compared them to the sequences of three E strains and two J strains retrieved from GenBank (including the Oka vaccine preparation, V-Oka). Except for a few polymorphic tandem repeat regions, the whole genome, representing approximately 125,000 nucleotides, is highly conserved, presenting a genetic similarity between the E and J genotypes of approximately 99.85%. These analyses revealed that VZV strains distinctly segregate into at least four genotypes (E, J, M1, and M2) in phylogenetic trees supported by high bootstrap values. Separate analyses of informative sites revealed that the tree topology was dependent on the region of the VZV genome used to determine the phylogeny; collectively, these results indicate the observed strain variation is likely to have resulted, at least in part, from interstrain recombination. Recombination analyses suggest that strains belonging to the M1 and M2 genotypes are mosaic recombinant strains that originated from ancestral isolates belonging to the E and J genotypes through recombination on multiple occasions. Furthermore, evidence of more recent recombination events between M1 and M2 strains is present in six segments of the VZV genome. As such, interstrain recombination in dually infected cells seems to figure prominently in the evolutionary history of VZV, a feature it has in common with other herpesviruses. In addition, we report here six novel genomic targets located in open reading frames 51 to 58 suitable for genotyping of clinical VZV isolates.
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| 17. |
- Norberg, Peter, 1974, et al.
(författare)
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Divergence and recombination of clinical herpes simplex virus type 2 isolates.
- 2007
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Ingår i: Journal of virology. - 1098-5514. ; 81:23, s. 13158-67
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Forskningsöversikt (refereegranskat)abstract
- Herpes simplex virus type 2 (HSV-2) infects the genital mucosa and is one of the most common sexually transmitted viruses. Here we sequenced a segment comprising 3.5% of the HSV-2 genome, including genes coding for glycoproteins G, I, and E, from 27 clinical isolates from Tanzania, 10 isolates from Norway, and 10 isolates from Sweden. The sequence variation was low compared to that described for clinical HSV-1 isolates, with an overall similarity of 99.6% between the two most distant HSV-2 isolates. Phylogenetic analysis revealed a divergence into at least two genogroups arbitrarily designated A and B, supported by high bootstrap values and evolutionarily separated at the root. Genogroup A contained isolates collected in Tanzania, and genogroup B contained isolates collected in Tanzania and Scandinavia, implying that the genetic variability of HSV-2 is higher in Tanzania than in Scandinavia. Recombination network analysis and bootscan analysis revealed a complex pattern of phylogenetically conflicting informative sites in the sequence alignments. These signals were present in synonymous and nonsynonymous sites in all three genes and were not accumulated in specific regions, observations arguing against positive selection. Since the PHI test applied solely to synonymous sites revealed a high statistical probability of recombination, we suggest as a novel finding that homologous recombination is, as reported earlier for HSV-1 and varicella-zoster virus, a prominent feature in the evolution of HSV-2.
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| 18. |
- Norberg, Peter, 1974, et al.
(författare)
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Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction enzymes.
- 2006
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 44:12, s. 4511-4
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Tidskriftsartikel (refereegranskat)abstract
- Recently, three distinct genotypes of clinical herpes simplex virus type 1 (HSV-1) isolates were identified based on DNA sequence information and phylogenetic analysis of clinical isolates and laboratory strains. We utilized single-nucleotide polymorphism within the genes coding for glycoproteins G and I for rapid genotype classification by PCR and restriction enzyme cleavage. The method is suitable for high-scale genotyping of clinical HSV-1 isolates and for the detection of recombinants.
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| 19. |
- Norberg, Peter, 1974, et al.
(författare)
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Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.
- 2007
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88:Pt 6, s. 1683-8
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. Assessment of the O-glycosylation capacity of an acceptor peptide (STPSTTTSTPSTTT), representing two of the gI blocks, showed that the peptide was a universal substrate for O-glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin region has not been described previously for HSV-1 and is a unique finding, as repeated blocks within gI homologues are lacking in other alphaherpesviruses.
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| 20. |
- Norberg, Peter, 1974, et al.
(författare)
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Phylogenetic analysis of clinical herpes simplex virus type 1 isolates identified three genetic groups and recombinant viruses.
- 2004
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Ingår i: Journal of virology. - 0022-538X. ; 78:19, s. 10755-64
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.
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| 21. |
- Norberg, Åke
(författare)
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Clinical pharmacokinetics of intravenous ethanol : relationship between the ethanol space and total body water
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Total body water (TBW) is an important parameter in pathological states where the normal regulation of fluid balance is impaired (e.g., during critical illness, congestive heart failure, bum injury and renal insufficiency). Dilution of water isotopes, such as deuterium oxide (D2O), is considered die gold standard method for measuring TBW in humans. However this procedure requires skilled staff, expensive equipment and the results are seldom available in a timely fashion, which makes it less suitable for clinical applications. Ethanol is completely miscible with water and is thought to distribute into the TBW. The ethanol volume of distribution at steady state (Vss) can be estimated by pharmacokinetic analysis of the concentration-time profile. Ethanol can be measured in expired breath with high precision and this non- invasive method of analysis could provide an attractive alternative with the prospect of bedside monitoring of Vss within 4-6 hours. The aim. of this thesis was to develop an appropriate pharmacokinetic model for intravenous ethanol administration and to identify experimental factors that impact on the results. With this background, we compared Vss. determined by ethanol dilution with TBW determined by D20 dilution. The complicated absorption kinetics of ethanol (e.g. variable gastric emptying and first-pass metabolism) was avoided by use of the intravenous route of administration. Material and Methods: Forty-six healthy volunteers (20 women and 26 men) received intravenous infusions of ethanol (0.4- 0.6 g/kg body weight) in 15-60 minutes. The concentration of ethanol was measured in end-expired breath by infrared spectrometry and in blood and urine by headspace gas chromatography. Specimens of blood and breath were obtained at 5-15 min intervals for 3-6 hours post-dosing. The concentration of D20 in plasmawater was measured with isotope ratio mass spectrometry. Subjective feelings of inebriation were measured with a visual analogue scale. A number of pharmacokinetic models were developed and evaluated in the course of this thesis. The effect of eating a meal on ethanol kinetics was investigated in crossover studies by giving the same dose of ethanol in fed and fasted states. The magnitude and time-course of arterio-venous differences in ethanol concentration were determined to assess the importance of local peripheral vasodilatation and vasoconstriction on results. This was achieved by warming the sampling hand in a heating box or cooling the hand in cold water during ethanol infusion experiments. The impact of ~ling site on pharmacokinetic parameters of ethanol was investigated by simultaneous sampling in expired breath, arterial blood and venous blood. Inter- and intra-individual variations in precision of the estimates of Vss. and TBW were studied by making repeat infusions of ethanol a few days apart, and use of analysis of variance. Results and discussion: The two-compartment model with parallel Michaelis-Menten kinetics and first-order rend elimination provided an excellent prediction of the entire concentration-time profiles of ethanol and proved to be theoretically superior to the other kinetic models tested. A good reproducibility was obtained for all pharmacokinetic parameters, especially for Vss and the maximal metabolic rate (Vmax). Eating a meal increased the rate of ethanol metabolism by 30-60% and this confounding factor needs to be considered in clinical studies when Vss. for ethanol is estimated. Peripheral vasoconstriction caused a lowering of the concentrations of ethanol in venous blood, which also impacts on the pharmacokinetic parameters of ethanol. Measuring ~1 in breath agreed more closely with arterial blood concentrations than with venous blood. The pharmacokinetic parameters of ethanol could be measured with equally high precision in expired breath and venous blood. An ethanol dose of 0.4 g/kg body weight infused in 15 minutes led to unacceptable inebriation in some volunteer subjects. The precision of estimating Vss by ethanol dilution was about the same as for measuring TBW by D20 dilution (SD 0.8-.1.1 litres). However, me observed a systematic bias of -13% between Vss and TBW (D20). A likely explanation for this finding might be that water in the body, at least in part, is structured in such a way that ethanol is prevented from complete equilibration. Conclusions: A two-compartment model with parallel Michaelis-Menten and first-order renal elimination gave an excellent fit to the concentration-time profile of ethanol after intravenous ~on. Feeding state and peripheral circulation affected the estimated model parameters. Sampling and analysis of breath provided results with the same high precision as venous blood for estimating ethanol Vss. The non-invasive nature of breath sampling makes it more suitable for clinical purposes. The systematic bias of-13% between the Vss and TBW by D20 dilution suggests that ethanol does not distribute uniformly into the TBW. The reason for this discrepancy remains to be established.
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| 22. |
- Norberg, Åke, et al.
(författare)
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Do ethanol and deuterium oxide distribute into the same water space in healthy volunteers?
- 2001
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Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 25:10, s. 1423-1430
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Tidskriftsartikel (refereegranskat)abstract
- Background: The volume of distribution at steady state for ethanol (VSS) is thought to be identical to the total body water (TBW). We compared a two-compartment pharmacokinetic model with parallel Michaelis-Menten and first-order renal elimination with the classical one-compartment zero-order elimination model. Ethanol concentration-time profiles were established for breath, venous blood, and urine. The values of VSS obtained for ethanol were compared with TBW determined by deuterium oxide dilution. Methods: Sixteen healthy volunteers each received a 30-min intravenous infusion of ethanol on two occasions. Ethanol was measured in breath by a quantitative infrared analyzer and in blood and urine by headspace gas chromatography. Deuterium oxide was given as an intravenous injection and measured in serum by isotope-ratio mass spectrometry. Components of variation were calculated by ANOVA to determine the precision of the estimates of VSS and TBW. Results: Mean TBW, determined by deuterium oxide dilution, was 44.1 ▒ 3.9 liters (▒SD) for men, corresponding to 0.61 liters/kg, and 37.4 ▒ 3.2 liters for women, or 0.54 liters/kg. Estimates of VSS from blood-ethanol pharmacokinetics were 87.6% of TBW according to isotope dilution and 84.4% for breath analysis with the two-compartment model. This compares with 95.1% and 95.4% for blood and breath alcohol, respectively, when the classical zero-order kinetic analysis is used. The precision of the estimates of VSS and TBW was between ▒1.56 and ▒2.19 liters (95% confidence interval). Conclusions: Ethanol does not distribute uniformly into the TBW. The precision of measuring VSS by ethanol dilution was comparable to estimates of TBW by isotope dilution. Results of noninvasive breath ethanol analysis compared well with use of venous blood for estimating VSS. The sophisticated two-compartment model was much superior to the classical one-compartment model in explaining the total concentration-time course of intravenously given ethanol.
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| 23. |
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| 24. |
- Norberg, Åke, 1939, et al.
(författare)
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Evolution of enlarged body size of coal tits Parus ater in geographic isolation from two larger competitors, the crested tit Parus cristatus and the willow tit Parus montanus, on six Scandinavian islands
- 2015
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 4:11, s. 1490-1508
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report that on six widely separated Scandinavian islands, the coal tit Parus ater has evolved morphologically in the direction of two absent competitors, the crested tit P. cristatus and the willow tit P. montanus, to the effect that it is up to 10% larger in linear dimensions than conspecifics on the adjacent Swedish mainland, where all three species coexist. The large size is genetically determined, as ascertained by clutch exchange experiments between island and mainland nests. We conclude that the increased size of P. ater in places where it is geographically isolated from its larger congeners is the result of evolutionary adaptation, due ultimately to relaxed interspecific competition. On the islands, P. ater has evolved into a medium-sized generalist, with selection pressures likely governed by the following causal relationships. When competitors are lacking, P. ater takes over the foraging space of the absentees. The enlarged food base allows higher population densities, which intensifies intraspecific interference competition. This, in turn, selects for increased body size. When P. ater coexists with its larger congeners, it occupies peripheral foraging sites in trees, which requires excellent manoeuvrability and energy-expensive locomotion modes. Reduction of body size increases locomotor capacity for mechanical and aerodynamic reasons and lowers energy consumption, so small size is favoured in sympatry. But in geographic isolation, P. ater exploits the tree periphery less and the inner tree regions more, and it also adopts the easier locomotion modes of the absent species. Therefore, selection for manoeuvrability and a small body size is relaxed. The new selection regime shifts the balance between opposing selection forces towards a larger body size. We were able to test 11 alternative hypotheses and available evidence conclusively eliminates them all. As a result, here, evolution could be predicted regarding both direction and amount of change.
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| 25. |
- Norberg, Åke
(författare)
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Isolation and characterization of regulatory peptides and bioactive compounds
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Isolation of peptides and other bioactive compounds is an important and often necessary step to get the total information about their structures. This is demonstrated by a number of different characterizations in this thesis. Bioactive peptides and small organic molecules can act as signaling substances and messengers in multicellular organisms and are fundamental to higher forms of life. The following bioactive peptides and compounds were studied. 1) Different assays can be used for detection of novel peptides. Chemical assays are simple, but still robust, and have proven successful in several cases. In this thesis, an assay was developed to detect peptides that contain tryptophan. An N-terminal dipeptide Gly-Trp is characteristic for galanin, which was cleaved off, separated and visualized. In this manner a novel form of galanin from chicken was detected and isolated. 2) Antibacterial peptides were first found in insects and later in mammals. Many of these peptides are basic, some are Pro/Arg-rich (e.g. peptide PR-39). Investigation of basic peptides from pig spleen, resulted in the isolation of a new variant form of NK-lysin, previously only detected in a cDNA library from porcine bone marrow. PR-39 was identified by a method suitable for Pro/Arg-rich peptides using ladder sequence analysis with mass spectrometry. 3) Another biological assay, involving cAMP production in cell culture of SK-N-MC cells, was used to screen peptide fractions, and resulted in the isolation of a novel form of the hormone PYY, with a phosphate group attached to the Ser-13 residue. This finding demonstrates the benefit of peptide isolation to find posttranslational modifications not directly obvious from the corresponding DNA sequence. Using nano-electrospray tandem mass spectrometry, the phosphorylated form of porcine PYY was identified and the modification localized to Ser-13. 4) Specific antibodies raised against peptides are a valuable tool in peptide chemistry. We have isolated PEC-60 from pig and rat brains with a method that combines column purification procedures with the specificity of a radioimmunoassay (RIA) and the sensitivity of mass spectrometry to directly identify the peptide. The results show that PEC-60, like many other peptides, is localized in the gastrointestinal tract and also in the central nervous system. The specific regional brain distribution may imply a specific function. 5) Using RIA and HPLC purification, 4 novel forms of modified galanin were isolated and characterized by mass spectrometry. The modified forms contained beta-aspartic shifts and oxidized tyrosine. 6) Hypoglycemic agents have been described in plants. Gynostemma pentaphyllum (Cucurbitaceae), an East-Asian herb, has been reported to have different activities, such as antitumor, cholesterol-lowering, immunopotentiating, hypoglycemic and antioxidant effects. We have isolated a novel insulin-releasing substance from this extract, determined the structure by NMR and mass spectrometry and characterized the effects on insulin release. We found that it is a novel saponin and we named it phanoside. The results provide us with new knowledge about localization, structure, and processing of hormones and bioactive molecules.
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| 26. |
- Norberg, Åke, et al.
(författare)
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Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers
- 2007
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Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 107:1, s. 24-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts.METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored.RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged.CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.
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| 27. |
- Norberg, Åke, 1939, et al.
(författare)
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Scaling for stress similarity and distorted-shape similarity in bending and torsion under maximal muscle forces concurs with geometric similarity among different-sized animals
- 2010
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Ingår i: JOURNAL OF EXPERIMENTAL BIOLOGY. - 0022-0949. ; 213:16, s. 2873-2888
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Tidskriftsartikel (refereegranskat)abstract
- When geometric similarity, or isometry, prevails among animals of different sizes their form and proportions are similar. Weight increases as the cube of the length dimension, while cross-sectional areas increase as its square, so in load-bearing structural elements the stress, caused by the body weight, increases in direct proportion to the length dimension, both for pure axial loads and for transverse bending and torsional loads. On this account, large body sizes would be expected to set up compensatory selection on the proportions of supporting structures, making them disproportionately thicker as required to maintain similar, size-independent safety factors against breakage. Most previous scaling theories have assumed that the strength of support elements has evolved with respect to loads due to the body weight. But then, from the arguments above, a scaling principle different from the geometric similarity rule would be required in order for safety factors to remain similar among different-sized animals. Still, most comparable animals of ‘similar kind’ scale in accordance with the geometric similarity rule. Here, we instead argue that muscle forces cause much larger loads on structural support elements during maximum performance events (such as during prey capture or escape from predators) than do loads dictated by the body weight (such as during cruising locomotion), and that structural strength therefore might evolve with respect to maximal muscle forces rather than to the body weight. We explore how the transverse and longitudinal lengths of structural support elements must scale to one another, and to muscle transverse length, in order to satisfy each of the following, functionally based, similarity principles for support elements placed in bending, or in torsion, by maximal muscle forces during locomotion: (1) similarity in axial stress, or (2) in torsional shear stress, and (3) similarity in bent shape, or (4) in twisted shape. A dimensional relationship that satisfies all four conditions actually turns out to be the geometric similarity rule. These functional attributes may therefore help to explain the prevalence of geometric similarity among animals. Conformance of different-sized species with the geometric similarity principle has not been directly selected for as such, of course, but may have arisen as a by-product of adaptation in morphological proportions, following upon selection, in each separate species-lineage, for adequate and similar safety factors against breakage, and similar optimal distorted shapes, of structural support elements placed in bending, or in torsion, by maximal muscle forces.
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| 28. |
- Norberg, Åke, 1939
(författare)
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Test of theory of foraging mode: Goldcrests, Regulus regulus, forage by high-yield, energy-expensive hovering flight when food is abundant but use low-yield, low-cost methods when food is scarce
- 2021
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 11:23, s. 16547-16561
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Tidskriftsartikel (refereegranskat)abstract
- Here, I describe foraging behavior of goldcrests, Regulus regulus, based on eight years of field observation in a coniferous forest dominated by Norway spruce Picea abies in southwestern Sweden. The aim was to test predictions from theory on the choice of optimal foraging modes in relation to food availability. Mortality from early November to early March amounts to 70-86% among goldcrests in the resident population, suggesting they are food-limited in winter. Food-limitation manifests itself as a shortage of time for foraging. It promotes the use of foraging methods that minimize the daily foraging time by maximizing the rate of net energy gain. It increases both individual survival and competitiveness. Elimination of competitors by exploitation occurs when an individual is able to support itself, while food density in the habitat is reduced to levels at which others cannot. Theory shows that when food is abundant, high-efficiency energy-expensive search and capture methods give shorter daily foraging times than low-efficiency low-cost methods, whereas the latter gives shorter daily foraging times at food shortages (Norberg 2021). Hovering flight is extremely expensive in energy but results in high foraging efficiency. Hover-foraging should therefore be used when food is abundant. In autumn, there were 85.3 arthropods per kilogram of branch mass, as opposed to 12.9 in spring. The numerical decline of arthropods, their fat metabolism, and size-biased predation by birds reduced the spring density of food for goldcrests to less than 15.1% of the autumn density. Hover-foraging occurred 5.29 times per minute in autumn but only 0.23 times per minute in spring, which is 4.4% of the autumn frequency. Foraging conditions are favorable at midsummer because of long days, high temperatures, and an abundance of arthropod prey. Parent birds that were feeding fledglings gathered food at a high rate and hovered 5.42 times per minute. But adults with no young to feed were not compelled to maximize the rate of net energy gain and only hover-foraged 0.52 times per minute, which is 10% of that of providers. These results are highly consistent from year to year and in qualitative agreement with theory.
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| 29. |
- Norberg, Åke, 1939
(författare)
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To minimize foraging time, use high-efficiency, energy-expensive search and capture methods when food is abundant but low-efficiency, low-cost methods during food shortages
- 2021
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 11:23, s. 16537-16546
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Tidskriftsartikel (refereegranskat)abstract
- Based on a mathematical model, I show that the amount of food in the habitat determines which among alternative methods for search of prey, respectively, for pursuit-and-capture give the shortest daily foraging time. The higher the locomotor activity, the higher the rate of energy expenditure and the larger the habitat space a predator can search for prey per time unit. Therefore, I assume that the more efficient a foraging method is, the higher its rate of energy expenditure. Survival selection favors individuals that use foraging methods that cover their energy needs in the shortest possible time. Therefore, I take the optimization criterion to be minimization of the daily foraging time or, equivalently, maximization of the rate of net energy gain. When time is limiting and food is in short supply, as during food bottleneck periods, low-efficiency, low-cost foraging methods give shorter daily foraging times than high-efficiency, energy-expensive foraging methods. When time is limiting, food is abundant and energy needs are large, as during reproduction, high-efficiency high-cost foraging methods give shorter daily foraging times than low-efficiency low-cost foraging methods. When time is not limiting, food is abundant, and energy needs are small, the choice of foraging method is not critical. Small animals have lower rates of energy expenditure for locomotion than large animals. At a given food density and with similar diet, small animals are therefore more likely than large ones to minimize foraging time by using high-efficiency energy-expansive foraging methods and to exploit patches and sites that require energy-demanding locomotion modes. Survival selection takes place at food shortages, while low-efficiency low-cost foraging methods are used, whereas reproduction selection occurs when food is abundant and high-efficiency energy-expensive foraging methods do better. In seasonal environments, selection therefore acts on different foraging methods at different times. Morphological adaptation to one method may oppose adaptation to another. Such conflicts select against foraging and morphological specialization and tend to give species-poor communities of year-round resident generalists. But a stable year-round food supply favors specialization, niche narrowing, and dense species packing.
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| 30. |
- Norberg, Åke, et al.
(författare)
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Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and the combination of hemorrhage and fluid infusion in sheep
- 2005
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Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 102:5, s. 985-994
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts.METHODS: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion.RESULTS: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments.CONCLUSION: Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.
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| 31. |
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| 32. |
- Tang, Ka-Wei, 1983, et al.
(författare)
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Rad51 and rad52 are involved in homologous recombination of replicating herpes simplex virus DNA.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Replication of herpes simplex virus 1 is coupled to recombination, but the molecular mechanisms underlying this process are poorly characterized. The role of Rad51 and Rad52 recombinases in viral recombination was examined in human fibroblast cells 1BR.3.N (wild type) and in GM16097 with replication defects caused by mutations in DNA ligase I. Intermolecular recombination between viruses, tsS and tsK, harboring genetic markers gave rise to ∼17% recombinants in both cell lines. Knock-down of Rad51 and Rad52 by siRNA reduced production of recombinants to 11% and 5%, respectively, in wild type cells and to 3% and 5%, respectively, in GM16097 cells. The results indicate a specific role for Rad51 and Rad52 in recombination of replicating herpes simplex virus 1 DNA. Mixed infections using clinical isolates with restriction enzyme polymorphisms in the US4 and US7 genes revealed recombination frequencies of 0.7%/kbp in wild type cells and 4%/kbp in GM16097 cells. Finally, tandem repeats in the US7 gene remained stable upon serial passage, indicating a high fidelity of recombination in infected cells.
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| 33. |
- Wilbe, Maria, et al.
(författare)
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DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:8, s. e12332-
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Tidskriftsartikel (refereegranskat)abstract
- Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.
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