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  • Berlin Kolm, Sofia, et al. (author)
  • Genetic diversity, population structure and phenotypic variation in European Salix viminalis L. (Salicaceae)
  • 2014
  • In: Tree Genetics & Genomes. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 10:6, s. 1595-1610
  • Journal article (peer-reviewed)abstract
    • To investigate the potential of association genetics for willow breeding, Salix viminalis germplasm was assembled from UK and Swedish collections (comprising accessions from several European countries) and new samples collected from nature. A subset of the germplasm was planted at two sites (UK and Sweden), genotyped using 38 SSR markers and assessed for phenological and biomass traits. Population structure, genetic differentiation (F-ST) and quantitative trait differentiation (Q(ST)) were investigated. The extent and patterns of trait adaptation were assessed by comparing F-ST and Q(ST) parameters. Of the 505 genotyped diploid accessions, 27 % were not unique. Genetic diversity was high: 471 alleles was amplified; the mean number of alleles per locus was 13.46, mean observed heterozygosity was 0.55 and mean expected heterozygosity was 0.62. Bayesian clustering identified four subpopulations which generally corresponded to Western Russia, Western Europe, Eastern Europe and Sweden. All pairwise F-ST values were highly significant (p<0.001) with the greatest genetic differentiation detected between the Western Russian and the Western European subpopulations (F-ST = 0.12), and the smallest between the Swedish and Eastern European populations (F-ST = 0.04). The Swedish population also had the highest number of identical accessions, supporting the view that S. viminalis was introduced into this country and has been heavily influenced by humans. Q(ST) values were high for growth cessation and leaf senescence, and to some extent stem diameter, but low for bud burst time and shoot number. Overall negative clines between longitudinal coordinates and leaf senescence, bud burst and stem diameter were also found.
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  • Hallingbäck, Henrik, et al. (author)
  • Association mapping in Salix viminalis L. (Salicaceae) - identification of candidate genes associated with growth and phenology
  • 2016
  • In: Global Change Biology Bioenergy. - : Wiley. - 1757-1693 .- 1757-1707. ; 8:3, s. 670-685
  • Journal article (peer-reviewed)abstract
    • Willow species (Salix) are important as short-rotation biomass crops for bioenergy, which creates a demand for faster genetic improvement and breeding through deployment of molecular marker-assisted selection (MAS). To find markers associated with important adaptive traits, such as growth and phenology, for use in MAS, we genetically dissected the trait variation of a Salix viminalis (L.) population of 323 accessions. The accessions were sampled throughout northern Europe and were established at two field sites in Pustnas, Sweden, and at Woburn, UK, offering the opportunity to assess the impact of genotype-by-environment interactions (GxE) on trait-marker associations. Field measurements were recorded for growth and phenology traits. The accessions were genotyped using 1536 SNP markers developed from phenology candidate genes and from genes previously observed to be differentially expressed in contrasting environments. Association mapping between 1233 of these SNPs and the measured traits was performed taking into account population structure and threshold selection bias. At a false discovery rate (FDR) of 0.2, 29 SNPs were associated with bud burst, leaf senescence, number of shoots or shoot diameter. The percentage of accession variation explained by these associations ranged from 0.3% to 4.4%, suggesting that the studied traits are controlled by many loci of limited individual impact. Despite this, a SNP in the EARLY FLOWERING 3 gene was repeatedly associated (FDR<0.2) with bud burst. The rare homozygous genotype exhibited 0.4-1.0 lower bud burst scores than the other genotype classes on a five-grade scale. Consequently, this marker could be promising for use in MAS and the gene deserves further study. Otherwise, associations were less consistent across sites, likely due to their small estimates and to considerable GxE interactions indicated by multivariate association analyses and modest trait accession correlations across sites (0.32-0.61).
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  • Berner, J, et al. (author)
  • Altered respiratory pattern and hypoxic response in transgenic newborn mice lacking the tachykinin-1 gene
  • 2007
  • In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 103:2, s. 552-559
  • Journal article (peer-reviewed)abstract
    • Substance P is known to be involved in respiratory rhythm and central pattern-generating mechanisms, especially during early development. We therefore studied respiratory responses in transgenic newborn mice (Tac1−/−) lacking substance P and neurokinin A (NKA). In vivo, the effects of intermittent isocapnic hypoxia (IH) and hypercapnia were studied using whole body flow plethysmography at P2-3 and P8-10. In vitro, anoxic responses and the effects of hypocapnic and hypercapnic conditions were studied in brain stem-spinal cord preparations (C4 activity) at P2. Hypoxic challenge considerably modified the respiratory activity in transgenic mice displayed in vivo as an attenuated increase in tidal volume during IH. Transgenic mice also showed a more prominent posthypoxic frequency decline in vivo, and posthypoxic neuronal arrests appeared more often in vitro. We recognized two types of sigh activity: with or without a following pause. During IH, the amount of sighs with a pause decreased and those without increased, a redistribution that became stronger with age only in controls. Intermittent anoxia induced long-term facilitation effects in controls, but not in Tac1−/− animals, manifested as an increase in burst frequency in vitro and by an augmentation of ventilation during posthypoxic periods in vivo. Thus our data demonstrate that a functional substance P/NKA system is of great importance for the generation of an adequate respiratory response to hypoxic provocation in newborn mice and during early maturation. It also indicates that substance P (and/or NKA) is involved in the development of the plasticity of the respiratory system.
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  • BLENNOW, M, et al. (author)
  • Monoamine neurotransmitters and metabolites in the cerebrospinal fluid following perinatal asphyxia
  • 1995
  • In: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 67:6, s. 407-413
  • Journal article (peer-reviewed)abstract
    • While the release of neurotransmitters is involved in the pathophysiology of brain damage following birth asphyxia, it also plays a role in endogenous defense against such damage. Levels of monoamines and the main cerebral monoamine metabolites in the cerebrospinal fluid (CSF) were measured in asphyxiated and control infants within 24 h after birth. The results indicate an increased turnover of noradrenaline (NA) and dopamine following asphyxia. Furthermore, the NA stores in the brain seem to be exhausted in some cases. We conclude that this increase in catecholamine turnover to some extent explains the clinical symptoms of hypoxic-ischemic encephalopathy and that it may reflect an intrinsic adaptive capacity to perinatal distress.
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  • Bowman, John L, et al. (author)
  • Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome
  • 2017
  • In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:2, s. 287-304.15
  • Journal article (peer-reviewed)abstract
    • The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.
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  • Carbajal, Ricardo, et al. (author)
  • Pain Assessment In Ventilated And Non-ventilated Neonates In Nicus Across Europe : European Pain Audit In Neonates (europain Survey)
  • 2014
  • In: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A68-A68
  • Journal article (peer-reviewed)abstract
    • Background: Neonates undergo many painful procedures during their NICU stay. These may include tracheal intubation/ventilation, skin-breaking procedures, drainage/suctioning of body orifices or cavities. Inherent subjectivity and difficulties of neonatal pain assessment contribute to a wide variety of assessment tools and clinical practices. To date, these practices have been not studied at a large scale.Objective: To determine current clinical practices for neonatal pain assessment in NICUs across Europe.Methods: An epidemiological observational study on bedside pain assessment practices collected data for all neonates in participating NICUs until infants left the unit (discharge, death, transfer to another hospital) or for 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to a gestational age of 44 weeks were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected pain assessment data in 6680 neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, 58.5% of TV neonates, 45.0% of NIV neonates and 30.4% of SV neonates received bedside pain assessments (p < 0.001). Fig. shows pain assessments by country.Conclusions: Over half (58.5%) of TV neonates and less than half (45.0%) of NIV neonates had pain assessments performed in European NICUs. Wide variations in the rates of pain assessment exist among countries and an important improvement seems necessary.
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  • Carbajal, Ricardo, et al. (author)
  • Sedation And Analgesia For Neonates In Nicus Across Europe : The Europain Survey
  • 2014
  • In: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A64-A64
  • Journal article (peer-reviewed)abstract
    • Background: Pain and stress induced by mechanical ventilation, invasive procedures, or painful diseases supports the use of sedation/analgesia (S/A) in newborns admitted to Neonatal Intensive Care Units (NICUs). To date, these practices have not been studied at a large scale.Objective: To determine current clinical practices regarding the use of S/A drugs in NICUs across Europe.Methods: This epidemiological observational study on bedside clinical practices regarding S/A collected data for all neonates in participating NICUs until the infant left the unit (discharge, death, transfer) or for up to 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to 44 weeks gestation were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected data on 6680 eligible neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, more TV neonates [81.5% (n = 1746)] received S/A drugs than NIV neonates [17.8% (n = 266)] and SV neonates [9.3% (n = 282)]; p < 0.001. Fig. shows the rate of S/A use by country; table shows S/A drugs used.Conclusions: Most ventilated but few non-ventilated neonates (NIV and SV) receive S/A therapy in European NICUs. Wide variations in S/A use, drugs used, and mode of administration (continuous, bolus, or both) exist among countries.
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  • Carbajal, Ricardo, et al. (author)
  • Sedation and analgesia practices in neonatal intensive care units (EUROPAIN) : results from a prospective cohort study
  • 2015
  • In: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 3:10, s. 796-812
  • Journal article (peer-reviewed)abstract
    • Background: Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries.                                         Methods: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745.                                         Findings: From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35∙0 weeks (SD 4∙6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p<0∙0001). In the participating NICUs, the median use of sedation or analgesia was 89∙3% (70∙0–100) for neonates in the TV group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of 2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in the TV group were given neuromuscular blockers, which were administered as continuous infusions to 146 (7%) of these neonates. Pain assessments were recorded in 1250 (58%) of 2138, 672 (45%) of 1493, and 916 (30%) of 3017 neonates in the TV, NIV, and SV groups, respectively (p<0∙0001). In the univariate analysis, neonates given O-SH-GA in the TV group needed a longer duration of TV than did those who were not given O-SH-GA (mean 136∙2 h [SD 173∙1] vs 39∙8 h [94∙7] h; p<0∙0001). Multivariable and propensity score analyses confirmed this association (p<0∙0001).                        Interpretation: Wide variations in sedation and analgesia practices occur between NICUs and countries. Widespread use of O-SH-GA in intubated neonates might prolong their need for mechanical ventilation, but further research is needed to investigate the therapeutic and adverse effects of O-SH-GA in neonates, and to develop new and safe approaches for sedation and analgesia. 
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  • Cohen, G, et al. (author)
  • beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure
  • 2002
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:20, s. 13272-13277
  • Journal article (peer-reviewed)abstract
    • Nicotine exposure diminishes the protective breathing and arousal responses to stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance could underpin the well established association between smoking and the increased risk of sudden infant death syndrome. We show here that the protective responses to stress during sleep are partially regulated by particular nicotinic acetylcholine receptors (nAChRs). We compared responses of sleeping wild-type and mutant mice lacking the β2 subunit of the nAChR to episodic hypoxia. Arousal from sleep was diminished, and breathing drives accentuated in mutant mice indicating that these protective responses are partially regulated by β2-containing nAChRs. Brief exposure to nicotine significantly reduced breathing drives in sleeping wild-type mice, but had no effect in mutants. We propose that nicotine impairs breathing (and possibly arousal) responses to stress by disrupting functions normally regulated by β2-containing, high-affinity nAChRs.
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