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1.
  • Herbertsson, Lina, et al. (författare)
  • Bees increase seed set of wild plants while the proportion of arable land has a variable effect on pollination in European agricultural landscapes
  • 2021
  • Ingår i: Plant Ecology and Evolution. - : Societe Royale de Botanique de Belgique. - 2032-3913 .- 2032-3921. ; 154:3, s. 341-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Agricultural intensification and loss of farmland heterogeneity have contributed to population declines of wild bees and other pollinators, which may have caused subsequent declines in insect-pollinated wild plants.Material and methods: Using data from 37 studies on 22 pollinator-dependent wild plant species across Europe, we investigated whether flower visitation and seed set of insect-pollinated plants decline with an increasing proportion of arable land within 1 km.Key results: Seed set increased with increasing flower visitation by bees, most of which were wild bees, but not with increasing flower visitation by other insects. Increasing proportion of arable land had a strongly variable effect on seed set and flower visitation by bees across studies.Conclusion:Factors such as landscape configuration, local habitat quality, and temporally changing resource availability (e.g. due to mass-flowering crops or honey bee hives) could have modified the effect of arable land on pollination. While our results highlight that the persistence of wild bees is crucial to maintain plant diversity, we also show that pollen limitation due to declining bee populations in homogenized agricultural landscapes is not a universal driver causing parallel losses of bees and insect-pollinated plants. 
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2.
  • Lindström, Jonas, 1977-, et al. (författare)
  • Uppgifter om mäns och kvinnors försörjningsaktiviteter i häradsrättens protokoll, Snevringe (Västmanland), perioden 1720-1880
  • 2020
  • Annan publikationabstract
    • Uppgifter om mäns och kvinnors försörjningsaktiviteter i Snevringe (Västmanland) häradsrätts protokoll har transkriberats och analyserats, och källtext och källtrogna variabler registrerats bokstavstroget, av Jonas Lindström, Benny Jacobsson, Carl Mikael Carlsson, Karin Hassan Jansson, Linnea Henningsson, Maria Ågren, Sarah Vorminder och Örjan Kardell, inom forskningsprojektet Gender and Work.Kvalitetskontroll är utförd av Sofia Ling och Jonas Lindström.Analys av källmaterialet har gjorts av Benny Jacobsson, Carl Mikael Carlsson, Karin Hassan Jansson, Linnea Henningsson, Maria Ågren, Sarah Vorminder, Örjan Kardell inom projektet Gender and Work https://www.uu.se/gawMaterialet är sökbart i databasen GAW - https://gotham.ddb.umu.se/
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3.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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4.
  • Ahnquist, Johanna, et al. (författare)
  • Social determinants of health - A question of social or economic capital? Interaction effects of socioeconomic factors on health outcomes
  • 2012
  • Ingår i: Social Science and Medicine. - : Elsevier BV. - 1873-5347 .- 0277-9536. ; 74:6, s. 930-939
  • Tidskriftsartikel (refereegranskat)abstract
    • Social structures and socioeconomic patterns are the major determinants of population health. However, very few previous studies have simultaneously analysed the "social" and the "economic" indicators when addressing social determinants of health. We focus on the relevance of economic and social capital as health determinants by analysing various indicators. The aim of this paper was to analyse independent associations, and interactions, of lack of economic capital (economic hardships) and social capital (social participation, interpersonal and political/institutional trust) on various health outcomes. Data was derived from the 2009 Swedish National Survey of Public Health, based on a randomly selected representative sample of 23,153 men and 28,261 women aged 16-84 year, with a participation rate of 53.8%. Economic hardships were measured by a combined economic hardships measure including low household income, inability to meet expenses and lacking cash reserves. Social capital was measured by social participation, interpersonal (horizontal) trust and political (vertical/institutional trust) trust in parliament. Health outcomes included; (i) self-rated health, (i) psychological distress (GHQ-12) and (iii) musculoskeletal disorders. Results from multivariate logistic regression show that both measures of economic capital and low social capital were significantly associated with poor health status, with only a few exceptions. Significant interactive effects measured as synergy index were observed between economic hardships and all various types of social capital. The synergy indices ranged from 1.4 to 2.3. The present study adds to the evidence that both economic hardships and social capital contribute to a range of different health outcomes. Furthermore, when combined they potentiate the risk of poor health. (C) 2012 Elsevier Ltd. All rights reserved.
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5.
  • Ahnquist, Johanna, et al. (författare)
  • What has trust in the health-care system got to do with psychological distress? Analyses from the national Swedish survey of public health
  • 2010
  • Ingår i: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1464-3677 .- 1353-4505. ; 22:4, s. 250-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Mental health disorders are a rapidly growing public health problem. Despite the fact that lack of trust in the health-care system is considered to be an important determinant of health, there is scarcity of empirical evidence demonstrating its associations with health outcomes. This is the first study which aims to evaluate the association between trust in the health-care system and psychological distress. Cross-sectional study. The association between trust in the health-care system and psychological distress was analysed with multiple logistic regression analysis adjusting for other factors. A randomly selected representative sample of women and men aged 16-84 years from the Swedish population who responded to the 2006 Swedish National Survey of Public Health. A total of 26 305 men and 30 584 women participated in the study. None. The main outcome measure was psychological distress measured by the General Health Questionnaire. Very low trust in health-care services was associated with an increased risk for psychological distress among men (odds ratio = 1.59, 95% confidence intervals 1.25-2.02) and among women (odds ratio = 1.83, 95% confidence intervals 1.47-2.27) after controlling for age, country of birth, socioeconomic circumstances, long-term illness and interpersonal trust. Our results suggest that health-care system mistrust is associated with an increased likelihood of psychological distress. Although causal relationships cannot be established, patient mistrust of health-care providers may have detrimental implications on health. Public health policies should include strategies aimed at increasing access to health-care services, where trust plays a substantial role.
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6.
  • Ali, Sadiq Mohammad, et al. (författare)
  • Gender differences in daily smoking prevalence in different age strata: A population-based study in southern Sweden.
  • 2009
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 37:2, s. 146-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate gender differences in daily smoking prevalence in different age groups in southern Sweden. Methods: The 2004 public-health survey in Skåne is a cross-sectional study. A total of 27,757 persons aged 18-80 years answered a postal questionnaire, which represents 59% of the random sample. A logistic regression model was used to investigate the associations between gender and daily smoking according to age. The multivariate analysis was performed to investigate the importance of possible confounders (country of origin, education, snus use, alcohol consumption, leisure-time physical activity, and BMI) on the gender differences in daily smoking in different age groups. Results: 14.9% of the men and 18.1% of the women were daily smokers. Middle-aged respondents were daily smokers to a significantly higher extent than young and old respondents. The prevalence of daily smoking also varied according to other demographic, socioeconomic, health related behaviour, and BMI characteristics. The crude odds ratios of daily smoking were 1.79 (1.42-2.26) among women compared to men in the 18-24 years age group, and 0.95 (0.80-1.12) in the 65-80 years age group. These odds ratios changed to 2.00 (1.49-2.67) and 0.95 (0.76-1.18), respectively, when all confounders were included. CONCLUSIONS: For the first time in Sweden women have a higher prevalence of daily smoking than men. The odds ratios of daily smoking are highest among women compared to men in the youngest age group of 18-24 years and the odds ratios decrease with increasing age. The findings point to a serious public health problem. Strategic interventions targeting young women's tobacco smoking are needed.
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7.
  • Gietzen, Dorothy W., et al. (författare)
  • Indispensable Amino Acid-Deficient Diets Induce Seizures in Ketogenic Diet-Fed Rodents, Demonstrating a Role for Amino Acid Balance in Dietary Treatments for Epilepsy
  • 2018
  • Ingår i: Journal of Nutrition. - : AMER SOC NUTRITION-ASN. - 0022-3166 .- 1541-6100. ; 148:3, s. 480-489
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. Objective: We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. Methods: In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for amp;gt;= 7 d, and tested for seizures using various stimuli. Microchip analysis of rat APCs was also used to determine if changes in transcripts for structures relevant to seizurogenesis are affected by a ThrDev diet. Glutamate release was measured in microdialysis samples from APCs during the first meal after 7 d on a CD or a ThrDev diet. Results: Adult rats showed increased susceptibility to seizures in both chemical (58%) and electroshock (doubled) testing after 7 d on a ThrDev diet compared with CD (each trial, P amp;lt;= 0.05). Seizure-prone Mongolian gerbils had fewer seizures after receiving a KD, but exacerbated seizures (68%) after 1 meal of KD minus Thr (KD-T compared with CD, P amp;lt; 0.05). In kindled rats fed KD-T, both counts (19%) and severities (77%) of seizures were significantly elevated (KD-T compared with CD, P amp;lt; 0.05). Gene transcript changes were consistent with enhanced seizure susceptibility (7-21 net-fold increases, P = 0.045-0.001) and glutamate release into the APC was increased acutely (4-fold at 20 min, 2.6-fold at 60 min, P amp;lt; 0.05) after 7 d on a ThrDev diet. Conclusion: Seizure severity in rats and gerbils was reduced after KDs and exacerbated by ThrDev, both in KD- and CD-fed animals, consistent with the mechanistic studies. We suggest that a complete protein profile in KDs may improve IAA balance in the APC, thereby lowering the risk of seizures.
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8.
  • Graham, Emily B., et al. (författare)
  • Microbes as Engines of Ecosystem Function : When Does Community Structure Enhance Predictions of Ecosystem Processes?
  • 2016
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Microorganisms are vital in mediating the earth's biogeochemical cycles; yet, despite our rapidly increasing ability to explore complex environmental microbial communities, the relationship between microbial community structure and ecosystem processes remains poorly understood. Here, we address a fundamental and unanswered question in microbial ecology: 'When do we need to understand microbial community structure to accurately predict function?' We present a statistical analysis investigating the value of environmental data and microbial community structure independently and in combination for explaining rates of carbon and nitrogen cycling processes within 82 global datasets. Environmental variables were the strongest predictors of process rates but left 44% of variation unexplained on average, suggesting the potential for microbial data to increase model accuracy. Although only 29% of our datasets were significantly improved by adding information on microbial community structure, we observed improvement in models of processes mediated by narrow phylogenetic guilds via functional gene data, and conversely, improvement in models of facultative microbial processes via community diversity metrics. Our results also suggest that microbial diversity can strengthen predictions of respiration rates beyond microbial biomass parameters, as 53% of models were improved by incorporating both sets of predictors compared to 35% by microbial biomass alone. Our analysis represents the first comprehensive analysis of research examining links between microbial community structure and ecosystem function. Taken together, our results indicate that a greater understanding of microbial communities informed by ecological principles may enhance our ability to predict ecosystem process rates relative to assessments based on environmental variables and microbial physiology.
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9.
  • Granseth, Björn, et al. (författare)
  • The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)
  • 2015
  • Ingår i: Genes, Brain and Behavior. - : Wiley: 12 months. - 1601-1848 .- 1601-183X. ; 14:6, s. 477-485
  • Tidskriftsartikel (refereegranskat)abstract
    • Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinsons disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1(+/-) mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinsons disease. Thus, it appears likely that VGluT1-expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1(+/-) mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1(+/-) mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.
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10.
  • Klawonn, Anna, et al. (författare)
  • Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity
  • 2018
  • Ingår i: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression (cFos and FosB) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.
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11.
  • Klawonn, Anna, et al. (författare)
  • The Sigma-2 Receptor Selective Agonist Siramesine (Lu 28-179) Decreases Cocaine-Reinforced Pavlovian Learning and Alters Glutamatergic and Dopaminergic Input to the Striatum
  • 2017
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Drug addiction is a chronic, debilitating disease that affects millions of people around the world causing a substantial societal burden. Despite decades of research efforts, treatment possibilities remain limited and relapse represents the most treatmentresistant element. Neurosteroid sigma-1 receptors have been meticulously studied in psychostimulant reinforced Pavlovian learning, while the sigma-2 receptor subtype has remained unexplored. Recent development of selective sigma-2 receptor ligands have now made it possible to investigate if the sigma-2 receptor system is a potential target to treat drug addiction. We examined the effect of the sigma-2 receptor agonist Siramesine (Lu 28-179) on cocaine-associated locomotion, Pavlovian learning, and reward neurocircuitry using electrophysiology recordings and in vivo microdialysis. We found that Siramesine significantly attenuated conditioned place preference acquisition and expression, as well as it completely blocked cocaine-primed reinstatement. Siramesine, in a similar manner as the selective sigma-1 receptor antagonist BD 1063, decreased acute locomotor responses to cocaine. Immunohistochemistry suggests co-expression of progesterone receptor membrane component 1/sigma-2 receptors and vesicular glutamate transporter 1 in presynaptic boutons of the nucleus accumbens (NAc). Whole-cell voltage clamp recordings of neurons in the NAc indicated that Siramesine decreases the presynaptic release probability of glutamate. Further, we demonstrated, via in vivo microdialysis, that Siramesine significantly decreased cocaine-evoked dopamine release in the striatum of freely moving mice. Collectively, these findings demonstrate that sigma-2 receptors regulate neurocircuitry responsible for positive reinforcement and thereby play a role in cocaine-reinforced Pavlovian behaviors.
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12.
  • Lehikoinen, Aleksi, et al. (författare)
  • Declining population trends of European mountain birds
  • 2019
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 25:2, s. 577-588
  • Tidskriftsartikel (refereegranskat)abstract
    • Mountain areas often hold special species communities, and they are high on the list of conservation concern. Global warming and changes in human land use, such as grazing pressure and afforestation, have been suggested to be major threats for biodiversity in the mountain areas, affecting species abundance and causing distribution shifts towards mountaintops. Population shifts towards poles and mountaintops have been documented in several areas, indicating that climate change is one of the key drivers of species’ distribution changes. Despite the high conservation concern, relatively little is known about the population trends of species in mountain areas due to low accessibility and difficult working conditions. Thanks to the recent improvement of bird monitoring schemes around Europe, we can here report a first account of population trends of 44 bird species from four major European mountain regions: Fennoscandia, UK upland, south-western (Iberia) and south-central mountains (Alps), covering 12 countries. Overall, the mountain bird species declined significantly (−7%) during 2002–2014, which is similar to the declining rate in common birds in Europe during the same period. Mountain specialists showed a significant −10% decline in population numbers. The slope for mountain generalists was also negative, but not significantly so. The slopes of specialists and generalists did not differ from each other. Fennoscandian and Iberian populations were on average declining, while in United Kingdom and Alps, trends were nonsignificant. Temperature change or migratory behaviour was not significantly associated with regional population trends of species. Alpine habitats are highly vulnerable to climate change, and this is certainly one of the main drivers of mountain bird population trends. However, observed declines can also be partly linked with local land use practices. More efforts should be undertaken to identify the causes of decline and to increase conservation efforts for these populations.
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13.
  • Lindström, Sarah, et al. (författare)
  • Supporting ad-hoc re-planning and shareability at large-scale events
  • 2010
  • Ingår i: Proceedings of the 16th ACM International Conference on Supporting Group Work (GROUP '10). ACM, NewYork, NY.. - New York, New York, USA : ACM Press. - 9781450303873 ; , s. 245-252
  • Konferensbidrag (refereegranskat)abstract
    • I denna artikel presenterar vi resultat från ett forsknings- och utvecklingsprojekt som fokuserar på användningen av mobiltelefoner på en musikfestival. Vårt syfte är att undersöka hur festivalupplevelsen kan förbättras med införandet av mobila tjänster. Två frågor tas upp: Finns det några öppningar för nya tjänster som stödjer grupper vid storskaliga evenemang? Om så är fallet, vilka designutmaningar kan identifieras som viktiga att beakta för att förbättra festivalupplevelsen? Vår slutsats är att det finns flera öppningar för nya tjänster som stödjer grupper vid storskaliga evenemang. Vi identifierar två viktiga designutmaningar när man skapar nya tjänster: att stödja ad hoc-omplanering och delbarhet. Studien bidrar till utvecklingen av bättre anpassade tjänstedesigner och teknik i mobila miljöer, som denna musikfestival, samt andra storskaliga evenemang.
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14.
  • Lindström, Sarah, et al. (författare)
  • VGluT1 Deficiency Impairs Visual Attention and Reduces the Dynamic Range of Short-Term Plasticity at Corticothalamic Synapses
  • 2020
  • Ingår i: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 30:3, s. 1813-1829
  • Tidskriftsartikel (refereegranskat)abstract
    • The most common excitatory neurotransmitter in the central nervous system, glutamate, is loaded into synaptic vesicles by vesicular glutamate transporters (VGluTs). The primary isoforms, VGluT1 and 2, are expressed in complementary patterns throughout the brain and correlate with short-term synaptic plasticity. VGluT1 deficiency is observed in certain neurological disorders, and hemizygous (VGluT1(+/-)) mice display increased anxiety and depression, altered sensorimotor gating, and impairments in learning and memory. The synaptic mechanisms underlying these behavioral deficits are unknown. Here, we show that VGluT1(+/-) mice had decreased visual processing speeds during a sustained visual-spatial attention task. Furthermore, in vitro recordings of corticothalamic (CT) synapses revealed dramatic reductions in short-term facilitation, increased initial release probability, and earlier synaptic depression in VGluT1+/- mice. Our electron microscopy results show that VGluT1 concentration is reduced at CT synapses of hemizygous mice, but other features (such as vesicle number and active zone size) are unchanged. We conclude that VGluT1-haploinsuficiency decreases the dynamic range of gain modulation provided by CT feedback to the thalamus, and this deficiency contributes to the observed attentional processing deficit. We further hypothesize that VGluT1 concentration regulates release probability by applying a "brake" to an unidentified presynaptic protein that typically acts as a positive regulator of release.
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15.
  • Lindström, Åke, et al. (författare)
  • A Puzzling Migratory Detour: Are Fueling Conditions In Alaska Driving The Movement Of Juvenile Sharp-Tailed Sandpipers?
  • 2011
  • Ingår i: The Condor: ornithological applications. - : Oxford University Press (OUP). - 0010-5422. ; 113:1, s. 129-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Making a detour can be advantageous to a migrating bird if fuel-deposition rates at stopover sites along the detour are considerably higher than at stopover sites along a more direct route. One example of an extensive migratory detour is that of the Sharp-tailed Sandpiper (Calidris acuminata), of which large numbers of juveniles are found during fall migration in western Alaska. These birds take a detour of 1500-3400 km from the most direct route between their natal range in northeastern Siberia and nonbreeding areas in Australia. We studied the autumnal fueling rates and fuel loads of 357 Sharp-tailed Sandpipers captured in western Alaska. In early September the birds increased in mass at a rate of only 0.5% of lean body mass day(-1). Later in September, the rate of mass increase was about 6% of lean body mass day(-1), among the highest values found among similar-sized shorebirds around the world. Some individuals more than doubled their body mass because of fuel deposition, allowing non-stop flight of between 7100 and 9800 km, presumably including a trans-oceanic flight to the southern hemisphere. Our observations indicated that predator attacks were rare in our study area, adding another potential benefit of the detour. We conclude that the most likely reason for the Alaskan detour is that it allows juvenile Sharp-tailed Sand-pipers to put on large fuel stores at exceptionally high rates.
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16.
  • Lundgren, Markus, et al. (författare)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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17.
  • Mínguez‐Viñas, Teresa, et al. (författare)
  • Two epilepsy‐associated variants in KCNA2 (KV1.2) at position H310 oppositely affect channel functional expression
  • 2023
  • Ingår i: Journal of Physiology. - : WILEY. - 0022-3751 .- 1469-7793. ; 601:23, s. 5367-5389
  • Tidskriftsartikel (refereegranskat)abstract
    • Two KCNA2 variants (p.H310Y and p.H310R) were discovered in paediatric patients with epilepsy and developmental delay. KCNA2 encodes KV1.2-channel subunits, which regulate neuronal excitability. Both gain and loss of KV1.2 function cause epilepsy, precluding the prediction of variant effects; and while H310 is conserved throughout the KV-channel superfamily, it is largely understudied. We investigated both variants in heterologously expressed, human KV1.2 channels by immunocytochemistry, electrophysiology and voltage-clamp fluorometry. Despite affecting the same channel, at the same position, and being associated with severe neurological disease, the two variants had diametrically opposite effects on KV1.2 functional expression. The p.H310Y variant produced ‘dual gain of function’, increasing both cell-surface trafficking and activity, delaying channel closure. We found that the latter is due to the formation of a hydrogen bond that stabilizes the active state of the voltage-sensor domain. Additionally, H310Y abolished ‘ball and chain’ inactivation of KV1.2 by KVβ1 subunits, enhancing gain of function. In contrast, p.H310R caused ‘dual loss of function’, diminishing surface levels by multiple impediments to trafficking and inhibiting voltage-dependent channel opening. We discuss the implications for KV-channel biogenesis and function, an emergent hotspot for disease-associated variants, and mechanisms of epileptogenesis. 
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18.
  • Nilsson, Michelle, et al. (författare)
  • An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Significance: A child with epilepsy has a previously unreported, heterozygous mutation in KCNA2, the gene encoding KV1.2 proteins. Four KV1.2 assemble into a potassium-selective channel, a protein complex at the neuronal cell surface regulating electrical signaling. KV1.2 subunits assemble with other KV1-family members to form heterotetrameric channels, contributing to neuronal potassium-channel diversity. The most striking consequence of this mutation is preventing KV1.2-subunit trafficking, i.e., their ability to reach the cell surface. Moreover, the mutation is dominant negative, as mutant subunits can assemble with wild-type KV1.2 and KV1.4, trapping them into nontrafficking heterotetramers and decreasing their functional expression. Thus, KV1-family genes’ ability to form heterotetrameric channels is a double-edged sword, rendering KV1-family members vulnerable to dominant-negative mutations in a single member gene.Abstract: We report on a heterozygous KCNA2 variant in a child with epilepsy. KCNA2 encodes KV1.2 subunits, which form homotetrameric potassium channels and participate in heterotetrameric channel complexes with other KV1-family subunits, regulating neuronal excitability. The mutation causes substitution F233S at the KV1.2 charge transfer center of the voltage-sensing domain. Immunocytochemical trafficking assays showed that KV1.2(F233S) subunits are trafficking deficient and reduce the surface expression of wild-type KV1.2 and KV1.4: a dominant-negative phenotype extending beyond KCNA2, likely profoundly perturbing electrical signaling. Yet some KV1.2(F233S) trafficking was rescued by wild-type KV1.2 and KV1.4 subunits, likely in permissible heterotetrameric stoichiometries: electrophysiological studies utilizing applied transcriptomics and concatemer constructs support that up to one or two KV1.2(F233S) subunits can participate in trafficking-capable heterotetramers with wild-type KV1.2 or KV1.4, respectively, and that both early and late events along the biosynthesis and secretion pathway impair trafficking. These studies suggested that F233S causes a depolarizing shift of ∼48 mV on KV1.2 voltage dependence. Optical tracking of the KV1.2(F233S) voltage-sensing domain (rescued by wild-type KV1.2 or KV1.4) revealed that it operates with modestly perturbed voltage dependence and retains pore coupling, evidenced by off-charge immobilization. The equivalent mutation in the Shaker K+ channel (F290S) was reported to modestly affect trafficking and strongly affect function: an ∼80-mV depolarizing shift, disrupted voltage sensor activation and pore coupling. Our work exposes the multigenic, molecular etiology of a variant associated with epilepsy and reveals that charge-transfer-center disruption has different effects in KV1.2 and Shaker, the archetypes for potassium channel structure and function.
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19.
  • Pantazis, Antonios, et al. (författare)
  • Tracking the motion of the K(V)1.2 voltage sensor reveals the molecular perturbations caused by ade novomutation in a case of epilepsy
  • 2020
  • Ingår i: Journal of Physiology. - : WILEY. - 0022-3751 .- 1469-7793. ; 598:22, s. 5245-5269
  • Tidskriftsartikel (refereegranskat)abstract
    • Key points K(V)1.2 channels, encoded by theKCNA2gene, regulate neuronal excitability by conducting K(+)upon depolarization. A newKCNA2missense variant was discovered in a patient with epilepsy, causing amino acid substitution F302L at helix S4, in the K(V)1.2 voltage-sensing domain. Immunocytochemistry and flow cytometry showed that F302L does not impair KCNA2 subunit surface trafficking. Molecular dynamics simulations indicated that F302L alters the exposure of S4 residues to membrane lipids. Voltage clamp fluorometry revealed that the voltage-sensing domain of K(V)1.2-F302L channels is more sensitive to depolarization. Accordingly, K(V)1.2-F302L channels opened faster and at more negative potentials; however, they also exhibited enhanced inactivation: that is, F302L causes both gain- and loss-of-function effects. Coexpression of KCNA2-WT and -F302L did not fully rescue these effects. The probands symptoms are more characteristic of patients with loss ofKCNA2function. Enhanced K(V)1.2 inactivation could lead to increased synaptic release in excitatory neurons, steering neuronal circuits towards epilepsy. An exome-based diagnostic panel in an infant with epilepsy revealed a previously unreportedde novomissense variant inKCNA2, which encodes voltage-gated K(+)channel K(V)1.2. This variant causes substitution F302L, in helix S4 of the K(V)1.2 voltage-sensing domain (VSD). F302L does not affect KCNA2 subunit membrane trafficking. However, it does alter channel functional properties, accelerating channel opening at more hyperpolarized membrane potentials, indicating gain of function. F302L also caused loss of K(V)1.2 function via accelerated inactivation onset, decelerated recovery and shifted inactivation voltage dependence to more negative potentials. These effects, which are not fully rescued by coexpression of wild-type and mutant KCNA2 subunits, probably result from the enhancement of VSD function, as demonstrated by optically tracking VSD depolarization-evoked conformational rearrangements. In turn, molecular dynamics simulations suggest altered VSD exposure to membrane lipids. Compared to other encephalopathy patients withKCNA2mutations, the proband exhibits mild neurological impairment, more characteristic of patients withKCNA2loss of function. Based on this information, we propose a mechanism of epileptogenesis based on enhanced K(V)1.2 inactivation leading to increased synaptic release preferentially in excitatory neurons, and hence the perturbation of the excitatory/inhibitory balance of neuronal circuits.
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20.
  • Pasay, Sarah Linden, 1984- (författare)
  • Stable Media in the Age of Revolutions : Depictions of Economic Matters in British and Swedish State Newspapers, 1770–1820
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The dissertation examines how economic matters were depicted between 1770 and 1820 in two European kingdoms. Britain and Sweden are studied during this Age of Revolutions from the state’s perspective; state-managed newspapers are examined, one from Britain, the London Gazette, and two from Sweden, Stockholms Post-Tidningar and Inrikes Tidningar. These were stable types of media that transformed slowly alongside the changing popular press. State-managed newspapers were produced both to inform and manage the loyalty of populations. Aside from the continued development of the centralized state, this was also the time when Enlightenment ideals were spreading, the public sphere was transforming, notions of the nation and nationalism were developing, and communication strategies were changing; these concepts are the basis for the model of the development of modernity used in this study.Economic matters are seen as existing in a value-realm model that gradually disintegrated over time, expressing the birth of the modern world. This model included political, social-cultural, and technological values, in addition to economic matters. This disintegration involved a sense of uniformity. In both Britain and Sweden, economic objects, practices, ideas, and discourses received similar treatments over time. This process was, however, non-linear and not complete by the dawn of industrial transformation.  The first two chapters discuss the theory and methodological approaches. The form, order, and content of the newspapers are analyzed to show how economic matters became separate or unembedded to varying degrees over a fifty-year time span. British and Swedish descriptions are compared, as well as how the other state was portrayed in the opposing newspapers. These observations are described in three empirical chapters, relating events and analyses from 1770 to 1775, 1790 to 1795, and 1815 to 1820.The results of this dissertation show how early modern economic matters can be viewed beyond quantitative contents as an expression of becoming modern, offering complimentary context. Advances in thinking about data generated modern numerical indicators, also reflected by form and order qualities. The unembeddedness of economic matters was an ongoing and non-linear process that was expressed by increased abstractness, separation, and emphasis.
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21.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
  •  
22.
  • Senapathi, Deepa, et al. (författare)
  • Wild insect diversity increases inter-annual stability in global crop pollinator communities
  • 2021
  • Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 288:1947
  • Tidskriftsartikel (refereegranskat)abstract
    • While an increasing number of studies indicate that the range, diversity and abundance of many wild pollinators has declined, the global area of pollinator-dependent crops has significantly increased over the last few decades. Crop pollination studies to date have mainly focused on either identifying different guilds pollinating various crops, or on factors driving spatial changes and turnover observed in these communities. The mechanisms driving temporal stability for ecosystem functioning and services, however, remain poorly understood. Our study quantifies temporal variability observed in crop pollinators in 21 different crops across multiple years at a global scale. Using data from 43 studies from six continents, we show that (i) higher pollinator diversity confers greater inter-annual stability in pollinator communities, (ii) temporal variation observed in pollinator abundance is primarily driven by the three-most dominant species, and (iii) crops in tropical regions demonstrate higher inter-annual variability in pollinator species richness than crops in temperate regions. We highlight the importance of recognizing wild pollinator diversity in agricultural landscapes to stabilize pollinator persistence across years to protect both biodiversity and crop pollination services. Short-term agricultural management practices aimed at dominant species for stabilizing pollination services need to be considered alongside longer term conservation goals focussed on maintaining and facilitating biodiversity to confer ecological stability.
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23.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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24.
  • Sundberg, Sofie, et al. (författare)
  • Cre-expressing neurons in visual cortex of Ntsr1-Cre GN220 mice are corticothalamic and are depolarized by acetylcholine
  • 2018
  • Ingår i: Journal of Comparative Neurology. - : WILEY. - 0021-9967 .- 1096-9861. ; 526:1, s. 120-132
  • Tidskriftsartikel (refereegranskat)abstract
    • The Ntsr1-Cre GN220 mouse expresses Cre-recombinase in corticothalamic (CT) neurons in neocortical layer 6. It is not known if the other major types of pyramidal neurons in this layer also express this enzyme. By electrophysiological recordings in slices and histological analysis of the uptake of retrogradely transported beads we show that Cre-positive neurons are CT and not corticocortical or corticoclaustral types. Furthermore, we show that Ntsr1-Cre-positive cells are immuno-positive for the nuclear transcription factor Forkhead box protein P2 (FoxP2). We conclude that Cre-expression is limited to a specific type of pyramidal neuron: CT. However, it appears as not all CT neurons are Cre-expressing; there are indications that the penetrance of the gene is about 90%. We demonstrate the utility of assigning a specific identity to individual neurons by determining that the CT neurons are potently modulated by acetylcholine acting on both nicotinic and muscarinic acetylcholine receptors. These results corroborate the suggested function of these neurons in regulating the gain of thalamocortical transfer of sensory information depending on attentional demand and state of arousal.
  •  
25.
  • Surendran, Praveen, et al. (författare)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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26.
  • Uvnäs-Moberg, Kerstin, et al. (författare)
  • Maternal plasma levels of oxytocin during physiological childbirth : a systematic review with implications for uterine contractions and central actions of oxytocin
  • 2019
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies.METHODS: An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects.RESULTS: Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin.CONCLUSIONS: Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does.
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