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  • 51.
    Alriksson, Emelie
    Linköpings universitet, Institutionen för beteendevetenskap och lärande. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Höns återhämtning efter stress samt domesticeringens effekter: En biologisk studie med ett lärarperspektiv2011Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Den biologiska studien har visat att värphöns genom domesticeringen förändrat och anpassat sina beteenden till att leva med människor. De har utvecklat en minskad rädsla för människor och en ökad stresstålighet. I denna studie har höns återhämtning efter en stressupplevelse studerats. För att se hur domesticeringen har påverkat återhämtningen jämfördes beteenden mellan raserna White Leghorn och red junglefowl. Frågeställningarna som användes för att undersöka detta var: Hur lång tid tar det innan höns återhämtar sina naturliga beteenden, ej stressrelaterade, efter en stressupplevelse? Finns det några skillnader i återhämtningen beroende av kön eller mellan raserna White Leghorn och red junglefowl? Resultatet visade inte på en specifik tid för återhämtning men på att en tydlig återhämtning förekom. Återhämtningen visades i beteendena Relaxed Behaviour, Comfort Behaviour, Perch, Vocalisation och Stand Alert genom att uppvisandet av beteendena skiljde sig signifikant med tiden. Även signifikanta skillnader visades mellan raserna, både i beteenden som visade på återhämtning och i beteenden som inte gjorde det. En slutsats om vilken ras som återhämtade sig snabbast var svår att dra. Detta på grund av att beteendeskillnaderna visade på olika tendenser gällande återhämtning. Skillnaderna i återhämtningen mellan könen, visades tendenser på att hanarna återhämtade sig snabbare. Domesticering har även i denna studie studerats utifrån ett lärarperspektiv. Undersökningen visade att domesticering kan ingå i biologiundervisningen i områdena evolution och genetik i år 7-9.

  • 52.
    Alriksson, Felicia
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Individuell tillväxt och substratval hos en lokalt differentierad population av Asellus aquaticus2013Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    Local differentiation may occur during a short period of time and is part of the formation of new species. The isopod Asellus aquaticus is an example of a species in which local adaptation has occurred during a short period of time. An establishment of stonewort (Chara spp.) vegetation in Lake Tåkern (in the 2000) resulted in two different Asellus ecotypes; a lighter pigmented, smaller one that lives among stoneworts grazing periphytic algae, and a darker, larger ecotype that feeds on decaying leaves in reed (Phragmites australis vegetation. The purpose of this study was to examine whether there are differences in growth between ecotypes, depending on whether the food was periphytic algae or leaves, and to study the choice of substrates between the two food types. For the study, animals from both habitats were brought in from Lake Tåkern to the laboratory. I found that both the reed and the stonewort animals grew better when feeding on periphytic algae than on leaves, but that there was no difference in weight gain between the two ecotypes. There was no indication that the animals preferred any of the substrates. Results suggest that despite earlier noted differences in behavior, size and pigmentation (which differentiation had brought), there is no evidence that Asellus aquaticus has adapted to feed on plant matter prevailing in their original habitat. The animals grew better when the food was algae maybe due to that the algae, as previous studies show, are easier assimilated, whereas Asellus has to eat a larger amount of leaves to reach the same energy intake.

  • 53.
    Altimiras, Jordi
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Anderson, W. Gary
    University of Manitoba, Canada.
    Ecophysiology methods: Refining the old, validating the new and developing for the future2016Inngår i: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 202Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 54.
    Altimiras, Jordi
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Lindgren, Isa
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Giraldo-Deck, Lina Maria
    University of Mayor San Andres, Bolivia.
    Matthei, Alberto
    Tinamou Chile SL, Chile.
    Garitano-Zavala, Alvaro
    University of Mayor San Andres, Bolivia.
    Aerobic performance in tinamous is limited by their small heart. A novel hypothesis in the evolution of avian flight2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 15964Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Some biomechanical studies from fossil specimens suggest that sustained flapping flight of birds could have appeared in their Mesozoic ancestors. We challenge this idea because a suitable musculoskeletal anatomy is not the only requirement for sustained flapping flight. We propose the "heart to fly" hypothesis that states that sustained flapping flight in modern birds required an enlargement of the heart for the aerobic performance of the flight muscles and test it experimentally by studying tinamous, the living birds with the smallest hearts. The small ventricular size of tinamous reduces cardiac output without limiting perfusion pressures, but when challenged to fly, the heart is unable to support aerobic metabolism (quick exhaustion, larger lactates and post-exercise oxygen consumption and compromised thermoregulation). At the same time, cardiac growth shows a crocodilian-like pattern and is correlated with differential gene expression in MAPK kinases. We integrate this physiological evidence in a new evolutionary scenario in which the ground-up, short and not sustained flapping flight displayed by tinamous represents an intermediate step in the evolution of the aerobic sustained flapping flight of modern birds.

  • 55.
    Alvarez-Rodriguez, Manuel
    University of Leon, Facultad de Ciencias Biologicas y Ambientales, Spain.
    Mejora y evolución de los protocolos de congelación de eyaculados de oso pardo (Ursus arctos)2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [es]

    La situación crítica del oso pardo (Ursus arctos) en España plantea la necesidad de aplicar diferentes estrategias de conservación, dentro de las cuales tiene especial relevancia la creación de un banco de recursos genéticos. La eficacia de esta herramienta depende, entre otros factores, de la adaptación específica de los protocolos de congelación espermática ya existentes y que permitan el almacenamiento eficaz de los espermatozoides del oso pardo en un banco de germoplasma. Este trabajo nos permite concluir la utilidad de la selección entre ciclos con el fin de mejorar la calidad de los espermatozoides sometidos a recongelación

  • 56.
    Alvarez-Rodriguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Gomes-Alves, S
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Martinez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Quality of frozen-thawed semen in brown bear is not affected by timing of glycerol addition.2011Inngår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 75, nr 8, s. 1561-1565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have tested several freezing protocols for brown bear semen, modifying the time when glycerol was added (before and after cooling to 5 °C). No differences were found among protocols, indicating a good tolerance of brown bear semen to glycerol. This finding indicates that freezing protocols for brown bear semen could be modified to fit practical solutions which would facilitate preparation of the seminal samples in the field with the addition of glycerol at ambient temperature.

  • 57.
    Alvarez-Rodriguez, Manuel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Vicente-Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Exogenous Individual Lecithin-Phospholipids (Phosphatidylcholine and Phosphatidylglycerol) Cannot Prevent the Oxidative Stress Imposed by Cryopreservation of Boar Sperm.2017Inngår i: Journal of veterinary medicine and surgery, ISSN 2574-2868, Vol. 1, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Despite the use of high proportions of the chemically undefined lipoprotein/phospholipid-rich egg-yolk in extenders, boar sperm are highly sensitive to cooling, which induces ROS generation and disrupts the plasma membrane.

    Here, we studied whether replacement of hen egg-yolk by commercially defined lecithin phospholipids, derived from egg (LPGE: phosphatidyl glycerol, LPCE: phosphatidyl choline) or soybean (LPCS: phosphatidyl choline), could individually ameliorate such oxidative effects during cryopreservation of ejaculated (sperm rich fraction, SRF) or of cauda-epididymal sperm, retrieved post-mortem from the same males.

    Methods: A conventional extender (lactose buffer, with 20% egg-yolk, 0.5% OEP and 3% glycerol) was used as control. Cryodamage was assessed as loss of sperm motility, membrane and acrosome intactness, early membrane destabilization changes, mitochondrial potential, superoxide and ROS production, to finally determine lipid peroxidation (LPO) using specific probes.

    Results and conclusion: In general, the exogenous phospholipids assayed were unable of maintaining neither sperm motility nor viability post-thaw compared to controls, owing to increased ROS production and lipid peroxidation. In our study, mitochondrial superoxide production resulted in very high levels for all groups, whereas both ROS production and lipid peroxidation were reduced in the control group, containing emulsified hen egg yolk. Further studies using various dosage and combination of LPCS should be followed for their eventual protective effect.

    Keywords: Cryodamage; Sperm; Boar; Mitochondrial activation; Mitochondrial superoxide; ROS production; Lipid peroxidation

  • 58.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Anel-López, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Martínez-Rodríguez, Carmen
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    Martínez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    The antioxidant effects of soybean lecithin- or low-density lipoprotein-based extenders for the cryopreservation of brown-bear (Ursus arctos) spermatozoa.2013Inngår i: Reproduction, Fertility and Development, ISSN 1031-3613, E-ISSN 1448-5990, Vol. 25, nr 8, s. 1185-1193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Egg yolk low-density lipoproteins (LDL) and soybean lecithin were evaluated as replacements for egg yolk in extenders used for the cryopreservation of brown-bear spermatozoa. The motility, viability and acrosomal status of post-thawed spermatozoa were analysed, and an egg-yolk extender was used as a control. The total antioxidant capacity of these extenders was tested. Soybean lecithin showed an effect that was dependent on the soybean concentration (2%, 3.5% and 5%) and source (Type A: 24% L-α-phosphatidylcholine, and Type B: 14-23% L-α-phosphatidylcholine). Only semen cryopreserved with 5% Type A soybean exhibited a sperm motility similar to that of semen cryopreserved in egg-yolk-based extender after thawing, although the sperm viability and acrosome status were not as high. Semen frozen in an extender containing LDL (10-15%) exhibited improved sperm viability in comparison with the control, but sperm motility was lower. The LDL-based extender exhibited a higher anti-oxidant activity than the egg-yolk extender and soy lecithin-based extenders. The extenders with higher anti-oxidant activity showed improvements in frozen sperm viability but lower semen motility. These results indicate that soybean lecithin did not have the same protective effect as egg yolk during the freezing of brown-bear spermatozoa but suggest that LDL (10-15%) could be a useful substitute for egg yolk in these extenders.

  • 59.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain .
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Martinez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain .
    Holt, W V
    The Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK.
    Fazeli, Alireza
    The Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain .
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    The addition of heat shock protein HSPA8 to cryoprotective media improves the survival of brown bear (Ursus arctos) spermatozoa during chilling and after cryopreservation.2013Inngår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 79, nr 3, s. 541-550Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Cantabrian brown bear survives as a small remnant population in northern Spain and semen cryopreservation for future artificial insemination is one of the measures being implemented for conservation of this species. As part of this program we investigated the value of adding heat shock protein A8 (HSPA8) to media (N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid-TRIS-fructose with 20% egg yolk) used for chilling and cryopreserving the spermatozoa. Semen samples from eight brown bears were obtained by electroejaculation during the breeding season. In experiment 1, we tested three concentrations of HSPA8 (0.5, 1, and 5 μg/mL) to determine whether sperm motility (computer assisted sperm analysis system) and sperm survival could be improved during refrigeration (5 °C) up to 48 hours. Results showed that sperm viability (test with propidium iodide) was improved by the addition of 0.5 and 5 μg/mL HSPA8. In experiment 2, HSPA8 was added to the cryopreservation media (6% final glycerol concentration) before the freezing process. Though there were no differences in sperm viability immediately after thawing (analyses to 0 hours), plasma membrane permeability (test with YO-PRO-1) was significantly lower by the presence of HSPA8 (1 μg/mL) and acrosomal damage (test with peanut agglutinin-fluorescein isothiocyanate conjugate) was reduced by higher concentrations of HSPA8 (1 and 5 μg/mL) (analyses after thermal stress test incubating over 2 hours to 37 °C). In experiment 3, results of a simple progression test carried out through artificial mucus (hyaluronic acid 4 mg/mL) showed a significant decrease in the total number of sperm able to swim a distance of 0.5 to 2 cm through a capillary tube for all HSPA8-based extenders. Nevertheless, the distance traveled by the vanguard spermatozoa, which represent a highly motile subpopulation, was restored by the inclusion of 1 and 5 μg/mL HSPA8 in the cryopreservation media. Thus, the HSPA8 addition to extender improves the quality of brown bear (Ursus arctos) sperm during chilling (viability) and after cryopreservation (number of sperm with damaged acrosomes and "apoptotic-like" changes).

  • 60.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    López-Urueña, Elena
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Martínez-Rodriguez, Carmen
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cabárceno, Cantabria, Spain.
    Anel-López, Luis
    SaBio IREC (CSIC-UCLM-JCCM), Albacete, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Brown bear sperm double freezing: Effect of elapsed time and use of PureSperm(®) gradient between freeze-thaw cycles.2013Inngår i: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 67, nr 3, s. 339-346Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of sexed spermatozoa has great potential to captive population management in endangered wildlife. The problem is that the sex-sorting facility is a long distance from the semen collection place and to overcome this difficulty two freeze-thaw cycles may be necessary. In this study, effects of refreezing on brown bear electroejaculated spermatozoa were analyzed. We carried out two experiments: (1) to assess the effects of the two freezing-thawing cycles on sperm quality and to analyze three different elapsed times between freezing-thawing cycles (30, 90 and 180 min), and (2) to analyze the use of PureSperm between freezing-thawing cycles to select a more motile and viable sperm subpopulation which better survived first freezing. The motility, viability and undamaged acrosomes were significantly reduced after the second thawing respect to first thawing into each elapsed time group, but the elapsed times did not significantly affect the viability and acrosome status although motility was damaged. Our results with the PureSperm gradient showed higher values of viability in freezability of select sample (pellet) respect to the rest of the groups and it also showed a significant decrease in the number of acrosome damaged. In summary, the double freezing of bear semen selected by gradient centrifugation is qualitatively efficient, and thus could be useful to carry out a sex-sorting of frozen-thawed bear spermatozoa before to send the cryopreserved sample to a biobank. Given the low recovery of spermatozoa after applying a selection gradient, further studies will be needed to increase the recovery rate without damaging of the cell quality.

  • 61.
    Amarasinghe Vithanage, Dimali
    et al.
    Lund University, Sweden .
    Wang, Ergang
    Chalmers University of Technology, Göteborg, Sweden.
    Wang, Zhongqiang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Ma, Fei
    Lund University, Sweden .
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Andersson, Mats R.
    Chalmers University of Technology, Göteborg, Sweden.
    Yartsev, Arkady
    Lund University, Sweden .
    Sundström, Villy
    Lund University, Sweden .
    Pascher, Torbjörn
    Lund University, Sweden .
    Charge Carrier Dynamics of Polymer: Fullerene Blends: From Geminate to Non-Geminate Recombination2014Inngår i: Advanced Energy Materials, ISSN 1614-6832, Vol. 4, nr 8, artikkel-id 1301706Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The charge carrier dynamics of a new polymer-fullerene blend are examined on the femtosecond to the millisecond time scale. The full time range is globally fitted using a chemical reaction rate model that includes all key processes, charge generation, energy transfer, charge separation, and recombination, over the full 12 orders of magnitude in time and a factor of 33 in light intensity. Particular attention is paid to the charge recombination processes and it is found that they are highly material specific. Comparison of the dynamics to those of a previously studied polymer: fullerene blend reveals that while for one blend the recombination dynamics are mainly controlled by geminate recombination, the charge recombination in the presently studied polymer: fullerene blend are entirely controlled by non-geminate electron-hole recombination. Carrier density dependence of the non-geminate recombination rate is analyzed and a correlated disorder model of site energies is proposed to explain the observed dependency.

  • 62.
    Amiel, Joshua Johnstone
    et al.
    University of Sydney, Australia.
    Lindström, Tom
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Biologi. Linköpings universitet, Tekniska högskolan. University of Sydney, Australia.
    Shine, Richard
    University of Sydney, Australia.
    Egg incubation effects generate positive correlations between size, speed and learning ability in young lizards2014Inngår i: Animal Cognition, ISSN 1435-9448, E-ISSN 1435-9456, Vol. 17, nr 2, s. 337-347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have suggested that body size and locomotor performance are targets of Darwinian selection in reptiles. However, much of the variation in these traits may derive from phenotypically plastic responses to incubation temperature, rather than from underlying genetic variation. Intriguingly, incubation temperature may also influence cognitive traits such as learning ability. Therefore, we might expect correlations between a reptiles size, locomotor speed and learning ability either due to selection on all of these traits or due to environmental effects during egg incubation. In the present study, we incubated lizard eggs (Scincidae: Bassiana duperreyi) under hot and cold thermal regimes and then assessed differences in hatchling body size, running speed and learning ability. We measured learning ability using a Y-maze and a food reward. We found high correlations between size, speed and learning ability, using two different metrics to quantify learning (time to solution, and directness of route), and showed that environmental effects (incubation temperature) cause these correlations. If widespread, such correlations challenge any simple interpretation of fitness advantages due to body size or speed within a population; for example, survivors may be larger and faster than nonsurvivors because of differences in learning ability, not because of their size or speed.

  • 63.
    Amirhosseini, Mehdi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Aseptic Loosening of Orthopedic Implants: Osteoclastogenesis Regulation and Potential Therapeutics2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Aseptic loosening is the main cause of failure of orthopedic prostheses. With no pharmaceuticals to prevent or mitigate periprosthetic bone degradation, a surgery to replace the loose implant with a new one is the only choice to restore patients’ function. Most studies on mechanisms for aseptic loosening investigate wear debris particle-induced osteolysis. However, pathological loading conditions around unstable implants can also trigger osteoclast differentiation and bone loss.

    In the first study, global gene expression changes induced by mechanical instability of implants, and by titanium particles were compared in a validated rat model for aseptic loosening. Microarray analysis showed that similar signaling pathways and gene expression patterns are involved in particle- and instability-induced periprosthetic osteolysis with an early onset innate immune response as a hallmark of osteolysis induced by mechanical instability.

    Further, effects of potential therapeutics on restriction of excessive osteoclast differentiation were evaluated. Wnt signaling pathway is known to regulate bone remodeling. In the second study, effects of inactivation of glycogen synthase kinase 3 beta (GSK-3β), a negative regulator of canonical Wnt signaling, on instability-induced periprosthetic osteolysis were examined using our rat model for aseptic loosening. Inhibition of GSK-3β led to a decrease in osteoclast numbers in the periprosthetic bone tissue exposed to mechanical instability while osteoblast perimeter showed an increase. This was accompanied by higher bone volume fraction (BV/TV) in animals treated with the GSK-3β inhibitor.

    In the third study, potential beneficial effects of two selective inhibitors of cyclindependent kinase 8/19 (CDK8/19) on bone tissue were evaluated. CDK8/19 is a Mediator complex-associated transcriptional regulator involved in several signaling pathways. CDK8/19 inhibitors, mainly under investigation as treatments for tumors, are reported to enhance osteoblast differentiation and bone formation. We show in this study, for the first time, that inhibition of CDK8/19 led to marked suppression of osteoclast differentiation from bone marrow macrophages in vitro through disruption of the RANK signaling. In mouse primary osteoblasts downregulation of osteopontin mRNA, a negative regulator of mineralization, together with increased alkaline phosphatase activity and calcium deposition indicated that osteoblast mineralization was promoted by CDK8/19 inhibition. Moreover, local administration of a CDK8/19 inhibitor promoted cancellous bone regeneration in a rat model for bone healing.

    These studies contribute to better understanding of mechanisms behind mechanical instability-induced periprosthetic osteolysis and propose potential therapeutics to restrict bone loss with effects on both osteoclasts and osteoblasts.

    Delarbeid
    1. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    Åpne denne publikasjonen i ny fane eller vindu >>Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
    2017 (engelsk)Inngår i: Bone Reports, ISSN 2352-1872, Vol. 7, s. 17-25Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

    sted, utgiver, år, opplag, sider
    Elsevier, 2017
    Emneord
    Aseptic loosening; Implant; Instability; Microarray; Wear debris
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-146297 (URN)10.1016/j.bonr.2017.07.003 (DOI)28795083 (PubMedID)
    Tilgjengelig fra: 2018-04-07 Laget: 2018-04-07 Sist oppdatert: 2019-03-08
    2. GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Åpne denne publikasjonen i ny fane eller vindu >>GSK-3 beta inhibition suppresses instability-induced osteolysis by a dual action on osteoblast and osteoclast differentiation
    Vise andre…
    2018 (engelsk)Inngår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 233, nr 3, s. 2398-2408Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Currently, there are no medications available to treat aseptic loosening of orthopedic implants. Using osteoprotegerin fusion protein (OPG-Fc), we previously blocked instability-induced osteoclast differentiation and peri-prosthetic osteolysis. Wnt/beta-catenin signaling, which regulates OPG secretion from osteoblasts, also modulates the bone tissue response to mechanical loading. We hypothesized that activating Wnt/beta-catenin signaling by inhibiting glycogen synthase kinase-3 beta (GSK-3 beta) would reduce instability-induced bone loss through regulation of both osteoblast and osteoclast differentiation. We examined effects of GSK-3 beta inhibition on regulation of RANKL and OPG in a rat model of mechanical instability-induced peri-implant osteolysis. The rats were treated daily with a GSK-3 beta inhibitor, AR28 (20 mg/kg bw), for up to 5 days. Bone tissue and blood serum were assessed by qRT-PCR, immunohistochemistry, and ELISA on days 3 and 5, and by micro-CT on day 5. After 3 days of treatment with AR28, mRNA levels of beta-catenin, Runx2, Osterix, Col1 alpha 1, and ALP were increased leading to higher osteoblast numbers compared to vehicle-treated animals. BMP-2 and Wnt16 mRNA levels were downregulated by mechanical instability and this was rescued by GSK-3 beta inhibition. Osteoclast numbers were decreased significantly after 3 days of GSK-3 beta inhibition, which correlated with enhanced OPG mRNA expression. This was accompanied by decreased serum levels of TRAP5b on days 3 and 5. Treatment with AR28 upregulated osteoblast differentiation, while osteoclastogenesis was blunted, leading to increased bone mass by day 5. These data suggest that GSK-3 beta inactivation suppresses osteolysis through regulating both osteoblast and osteoclast differentiation in a rat model of instability-induced osteolysis.

    sted, utgiver, år, opplag, sider
    WILEY, 2018
    Emneord
    bone implant; GSK-3 beta; mechanical instability; osteolysis; Wnt signaling
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-148660 (URN)10.1002/jcp.26111 (DOI)000433519300056 ()28731198 (PubMedID)
    Merknad

    Funding Agencies|VINNOVA [2012-04409]; National Institutes of Health [AR056802]; Vetenskapsradet [K2014-7X-22506-01-3]; Swedish Research Council; Swedish Governmental Agency for Innovation Systems

    Tilgjengelig fra: 2018-06-18 Laget: 2018-06-18 Sist oppdatert: 2019-04-08
    3. Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Åpne denne publikasjonen i ny fane eller vindu >>Cyclin-dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing.
    Vise andre…
    2019 (engelsk)Inngår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, nr 9, s. 16503-16516Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Cyclin-dependent kinase 8 (CDK8) is a mediator complex-associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8-and its paralog CDK19-have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. CDK8/19 inhibitors did not alter the proliferation of neither mouse bone marrow-derived macrophages (BMMs) nor primary mouse osteoblasts. Receptor activator of nuclear factor κΒ (NF-κB) ligand (RANKL)-induced osteoclastogenesis from mouse BMMs was suppressed markedly by inhibition of CDK8/19, concomitant with reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen levels. This was accompanied by downregulation of PU.1, RANK, NF-κB, nuclear factor of activated T-cells 1 (NFATc1), dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K in RANKL-stimulated BMMs. Downregulating RANK and its downstream signaling in osteoclast precursors enforce CDK8/19 inhibitors as anticatabolic agents to impede excessive osteoclastogenesis. In mouse primary osteoblasts, CDK8/19 inhibition did not affect differentiation but enhanced osteoblast mineralization by promoting alkaline phosphatase activity and downregulating osteopontin, a negative regulator of mineralization. In rat tibiae, a CDK8/19 inhibitor administered locally promoted cancellous bone regeneration. Our data indicate that inhibitors of CDK8/19 have the potential to develop into therapeutics to restrict osteolysis and enhance bone regeneration.

    Emneord
    CDK8, RANK, osteoblasts, osteoclasts
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-154927 (URN)10.1002/jcp.28321 (DOI)000470174200186 ()30793301 (PubMedID)
    Merknad

    Funding agencies: Vetenskapsradet [521-2013-2593, 2016-06097, K2015-99x-10363-23-4, 2016-01822]; Swedish Research Council

    Tilgjengelig fra: 2019-03-05 Laget: 2019-03-05 Sist oppdatert: 2019-07-03
  • 64.
    Amundin, Mats
    et al.
    Kolmården Wildlife Park.
    Hållsten, Henrik
    Filosofiska institutionen, Stockholms universitet.
    Eklund, Robert
    Linköpings universitet, Institutionen för kultur och kommunikation, Avdelningen för språk och kultur. Linköpings universitet, Filosofiska fakulteten.
    Karlgren, Jussi
    Kungliga Tekniska Högskolan.
    Molinder, Lars
    Carnegie Investment Bank, Swedden.
    A proposal to use distributional models to analyse dolphin vocalisation2017Inngår i: Proceedings of the 1st International Workshop on Vocal Interactivity in-and-between Humans, Animals and Robots, VIHAR 2017 / [ed] Angela Dassow, Ricard Marxer & Roger K. Moore, 2017, s. 31-32Konferansepaper (Fagfellevurdert)
    Abstract [en]

    This paper gives a brief introduction to the starting points of an experimental project to study dolphin communicative behaviour using distributional semantics, with methods implemented for the large scale study of human language.

  • 65.
    Anandapadamanaban, Madhanagopal
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Structural insights into protein-protein interactions governing regulation in transcription initiation and ubiquitination2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Virtually every aspect of the cellular processes in eukaryotes requires that the interactions between protein molecules are well coordinated in different regulatory pathways. Any protein dysfunction involved in these regulatory pathways might lead to various pathological conditions. Understanding the structural and functional peculiarities of these proteins molecular machineries will help in formulating structure-based drug design.

    The first regulatory process studied here is the RNA polymerase-II mediated transcription of the eukaryotic protein-coding genes to produce mRNAs. This process requires the formation of the ‘transcription initiation’ by the assembly of Pre-Initiation Complex (PIC) formation at a core promoter region. Regulation at this initiation level is a key mechanism for the control of gene expression that governs cellular growth and differentiation. The transcription Factor IID (TFIID) is a conserved multiprotein general transcription factor with an essential role in  nucleating the PIC formation, composed of TATA Binding Protein (TBP) and about 14 TBP Associated Factors (TAFs). The here presented crystal structure (1.97Å) of TBP bound to TAND1 and TAND2 domains from TAF1 reveals a detailed molecular pattern of interactions involving both transcriptionally activating and repressing regions in TBP, thereby uncovering central principles for anchoring of TBP-binding motifs. Together with NMR and cellular analysis, this work provides the structural basis of competitive binding with TFIIA to modulate TBP in promoter recognition.

    In eukaryotes, another fundamental mechanism in the regulation of cellular physiology is the posttranslational modification of substrate proteins by ubiquitin, termed ‘ubiquitination’. Important actors in this mechanism are the ubiquitin-ligases (E3s) that culminate the transfer of ubiquitin to the substrate and govern the specificity of this system. One E3 ligase in particular, TRIM21, defines a subgroup of the Tripartite Motif (TRIM) family, which belongs to the major RING-type of E3 ubiquitin ligases, and plays an important role in pathogenesis of autoimmunity by mediating ubiquitination of transcription factors. The crystal structure (2.86Å) of the RING domain from TRIM21 in complex with UBE2E1, an E2 conjugating enzyme, together with the NMR and SAXS analysis as well as biochemical functional analysis, reveals the molecular basis for the dynamic binding interfaces. The TRIM21 mode of ubiquitin recognition and activation for catalytic transfer of ubiquitin can be modeled onto the entire TRIM family.

    Finally, we explored the concepts of conformational selection in proteins as a possible key component for protein-mediated transcriptional regulation. In this framework, MexR, a bacterial repressor of the MexAB-OprM efflux pump, and its mutant Arg21Trp were studied as an example for proteins presenting different conformations. The residue Arg21Trp mutation is clinically identified to cause of Multi-Drug Resistant (MDR) by attenuated DNA binding, and leads to the overexpression of the MexAB-OprM efflux pump. With the crystal structure (2.19Å) of MexR mutant Arg21Trp, in combination with MD-simulations and SAXS for both wild-type and mutant, we could unravel the atomic details of the wild-type conformations consisting in subsets of populations of DNA bound and unbound forms. Remarkably, the mutant Arg21Trp stabilize the DNA unbound state and shifts MexR in a pre-existing equilibrium, from a repressed to a derepressed state.

    Taken together, these studies substantially broaden our knowledge at a molecular level in protein interactions that are involved in transcriptional regulation and ubiquitination, studied by a carefully selected combination of complementary structural methods spanning different resolutions and time scales.

    Delarbeid
    1. High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation
    Åpne denne publikasjonen i ny fane eller vindu >>High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation
    Vise andre…
    2013 (engelsk)Inngår i: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 20, nr 8, s. 1008-+Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 angstrom) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBPs concave DNA-binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation.

    sted, utgiver, år, opplag, sider
    NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA, 2013
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-96977 (URN)10.1038/nsmb.2611 (DOI)000322715300016 ()
    Merknad

    Funding Agencies|Swedish Research Council|621-2011-6028621-2012-5250621-2012-5136|VINNOVA|P32045-1|Swedish Cancer Foundation|11 0681|Swedish Child Cancer Foundation|PROJ09/092|Forum Scientium Award||Canadian Institutes for Health Research|MT-13611|Japan Society for the Promotion of Science|23370077|Knut and Alice Wallenberg foundation||Canada Research Chair||

    Tilgjengelig fra: 2013-09-05 Laget: 2013-09-02 Sist oppdatert: 2017-12-06
    2. Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression
    Åpne denne publikasjonen i ny fane eller vindu >>Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression
    Vise andre…
    2016 (engelsk)Inngår i: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 24, nr 8, s. 1311-1321Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 angstrom) presented here is closely similar to wildtype MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members.

    sted, utgiver, år, opplag, sider
    CELL PRESS, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-131908 (URN)10.1016/j.str.2016.06.008 (DOI)000383244600012 ()27427478 (PubMedID)
    Merknad

    Funding Agencies|European Communitys Seventh Framework Program (FP7) under BioStruct-X [283570]; Swedish e-Science Research Center; Swedish Research Council; Tage Erlander Visiting Professor grant.

    The original status of this article was Manuscript and the titel was Population shift disengages DNA binding in a multidrug resistance MexR mutant.

    Tilgjengelig fra: 2016-10-13 Laget: 2016-10-11 Sist oppdatert: 2018-05-06
    3. Anti-Ro52 Autoantibodies from Patients with Sjögren's Syndrome Inhibit the Ro52 E3 Ligase Activity by Blocking the E3/E2 Interface
    Åpne denne publikasjonen i ny fane eller vindu >>Anti-Ro52 Autoantibodies from Patients with Sjögren's Syndrome Inhibit the Ro52 E3 Ligase Activity by Blocking the E3/E2 Interface
    Vise andre…
    2011 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, nr 42, s. 36478-36491Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Ro52 (TRIM21) is an E3 ligase of the tripartite motif family that negatively regulates proinflammatory cytokine production by ubiquitinating transcription factors of the interferon regulatory factor family. Autoantibodies to Ro52 are present in patients with lupus and Sjögren's syndrome, but it is not known if these autoantibodies affect the function of Ro52. To address this question, the requirements for Ro52 E3 ligase activity were first analyzed in detail. Scanning a panel of E2 ubiquitin-conjugating enzymes, we found that UBE2D1–4 and UBE2E1–2 supported the E3 ligase activity of Ro52 and that the E3 ligase activity of Ro52 was dependent on its RING domain. We also found that the N-terminal extensions in the class III E2 enzymes affected their interaction with Ro52. Although the N-terminal extension in UBE2E3 made this E2 enzyme unable to function together with Ro52, the N-terminal extensions in UBE2E1 and UBE2E2 allowed for a functional interaction with Ro52. Anti-Ro52-positive patient sera and affinity-purified anti-RING domain autoantibodies inhibited the E3 activity of Ro52 in ubiquitination assays. Using NMR, limited proteolysis, ELISA, and Ro52 mutants, we mapped the interactions between Ro52, UBE2E1, and anti-Ro52 autoantibodies. We found that anti-Ro52 autoantibodies inhibited the E3 ligase activity of Ro52 by sterically blocking the E2/E3 interaction between Ro52 and UBE2E1. Our data suggest that anti-Ro52 autoantibodies binding the RING domain of Ro52 may be actively involved in the pathogenesis of rheumatic autoimmune disease by inhibiting Ro52-mediated ubiquitination.

    sted, utgiver, år, opplag, sider
    American Society for Biochemistry and Molecular Biology, 2011
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-53170 (URN)10.1074/jbc.M111.241786 (DOI)000296538300033 ()
    Merknad

    Funding agencies|Swedish Research Council||Swedish Foundation for Strategic Research||VINNOVA||CeNano||Swedish Cancer Society||Karolinska Institutet||Linkoping University||King Gustaf Vs 80-Year Foundation||Heart-Lung Foundation||Stockholm County Council||Gustafsson Foundation||Soderberg Foundation||National Cancer Institute of Canada||Swedish Rheumatism Association||Wallenberg Foundation||

    Tilgjengelig fra: 2010-01-18 Laget: 2010-01-18 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    4. Structure of a TRIM21 - UBE2El complex reveals the specificity of E2 and ubiquitin recognition by TRIM E3 RINGs
    Åpne denne publikasjonen i ny fane eller vindu >>Structure of a TRIM21 - UBE2El complex reveals the specificity of E2 and ubiquitin recognition by TRIM E3 RINGs
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    TRIM21, a RlNG-containing E3 ubiquitin-ligase of the TRIM   protein family, is a major autoantigen in SLE and Sjögren's syndrome as well as a modifier of interferon regulatory factors, thereby regulating innate immune signalling. We herein report the 2.86 Å crystal structure ofhuman TRIM211-91 comprising the RING domain (residues 16-55), in complex with the human E2 conjugating UBE2El enzyme (also denoted UbcH6). The crystal structure, joint with analysis by NMR and SAXS as well as structure-directed mutations and functional assays provides a detailed view of the specificity-determining contacts that support specific E2 recognition in the TRIM family. A detailed comparison of our structure with known E2 bound ubiquitin complexes, supported by biochemical analyses, reveals the molecular basis for TRIM21 interactions with donor ubiquitin that activates catalytic ubiquitin transfer. Finally, our structure convincingly demonstrates the placement of the Ub-targeted Lys61 of the adjacent TRIM211- 91 close to the catalytically active UBE2El cysteine, and how the Lys61 amide is activated fora nucleophilic attack by hydrogen-bondeffected deshielding by conserved acidic residues at the E2 active site. In all, our structural findings provide molecular details ofthe selectivity involved in TRIM21 interactions with its cognate UBE2E1 enzyme and how TRIM21 positions ubiquitin in a catalytic conformation for ubiquitin transfer, and presents a snapshot of the Ub ligation step on a specific target residue of TRIM211-91 as an auto-ubiquitinated pseudo-substrate at high concentration. Increased structural and functional understanding of the TRIM mediated ubiquitination will aid development ofnovel therapeutic approaches in the entire TRIM family ofproteins.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-122466 (URN)
    Tilgjengelig fra: 2015-11-03 Laget: 2015-11-03 Sist oppdatert: 2015-11-13bibliografisk kontrollert
  • 66.
    Anandapadamanaban, Madhanagopal
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Kyriakidis, Nikolaos C.
    Karolinska Univ Hosp, Sweden; UDLA, Ecuador.
    Csizmok, Veronika
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wallenhammar, Amélie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Espinosa, Alexander C.
    Karolinska Univ Hosp, Sweden.
    Ahlner, Alexandra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Round, Adam R.
    Grenoble Outstn, France; European XFEL GmbH, Germany.
    Trewhella, Jill
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Univ Sydney, Australia.
    Moche, Martin
    Karolinska Inst, Sweden.
    Wahren-Herlenius, Marie
    Karolinska Univ Hosp, Sweden.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E22019Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 294, nr 30, s. 11404-11419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The E3 ubiquitin-protein ligase TRIM21, of the RING-containing tripartite motif (TRIM) protein family, is a major autoantigen in autoimmune diseases and a modulator of innate immune signaling. Together with ubiquitin-conjugating enzyme E2 E1 (UBE2E1), TRIM21 acts both as an E3 ligase and as a substrate in autoubiquitination. We here report a 2.82-angstrom crystal structure of the human TRIM21 RING domain in complex with the human E2-conjugating UBE2E1 enzyme, in which a ubiquitin-targeted TRIM21 substrate lysine was captured in the UBE2E1 active site. The structure revealed that the direction of lysine entry is similar to that described for human proliferating cell nuclear antigen (PCNA), a small ubiquitin-like modifier (SUMO)-targeted substrate, and thus differs from the canonical SUMO-targeted substrate entry. In agreement, we found that critical UBE2E1 residues involved in the capture of the TRIM21 substrate lysine are conserved in ubiquitin-conjugating E2s, whereas residues critical for SUMOylation are not conserved. We noted that coordination of the acceptor lysine leads to remodeling of amino acid side-chain interactions between the UBE2E1 active site and the E2-E3 direct interface, including the so-called linchpin residue conserved in RING E3s and required for ubiquitination. The findings of our work support the notion that substrate lysine activation of an E2-E3-connecting allosteric path may trigger catalytic activity and contribute to the understanding of specific lysine targeting by ubiquitin-conjugating E2s.

  • 67.
    Anandapadamanaban, Madhanagopal
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Kyriakidis, Nikolaos
    Rheumatology Unit, Department of Medicine, Center for Molecular Medicine L8:04, Karolinska Institutet, Stockholm, Sweden.
    Espinosa, Alexander
    Rheumatology Unit, Department of Medicine, Center for Molecular Medicine L8:04, Karolinska Institutet, Stockholm, Sweden.
    Round, Adam R.
    European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.
    Trewhella, Jill
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. School of Molecular Bioscience, The University of Sydney, New South Wales, Australia.
    Wahren-Herlenius, Marie
    Rheumatology Unit, Department of Medicine, Center for Molecular Medicine L8:04, Karolinska Institutet, Stockholm, Sweden.
    Moche, Martin
    Department of Medical Biochemistry and Biophysics, Protein Science Facility, Karolinska Institutet, Stockholm, Sweden.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Structure of a TRIM21 - UBE2El complex reveals the specificity of E2 and ubiquitin recognition by TRIM E3 RINGsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    TRIM21, a RlNG-containing E3 ubiquitin-ligase of the TRIM   protein family, is a major autoantigen in SLE and Sjögren's syndrome as well as a modifier of interferon regulatory factors, thereby regulating innate immune signalling. We herein report the 2.86 Å crystal structure ofhuman TRIM211-91 comprising the RING domain (residues 16-55), in complex with the human E2 conjugating UBE2El enzyme (also denoted UbcH6). The crystal structure, joint with analysis by NMR and SAXS as well as structure-directed mutations and functional assays provides a detailed view of the specificity-determining contacts that support specific E2 recognition in the TRIM family. A detailed comparison of our structure with known E2 bound ubiquitin complexes, supported by biochemical analyses, reveals the molecular basis for TRIM21 interactions with donor ubiquitin that activates catalytic ubiquitin transfer. Finally, our structure convincingly demonstrates the placement of the Ub-targeted Lys61 of the adjacent TRIM211- 91 close to the catalytically active UBE2El cysteine, and how the Lys61 amide is activated fora nucleophilic attack by hydrogen-bondeffected deshielding by conserved acidic residues at the E2 active site. In all, our structural findings provide molecular details ofthe selectivity involved in TRIM21 interactions with its cognate UBE2E1 enzyme and how TRIM21 positions ubiquitin in a catalytic conformation for ubiquitin transfer, and presents a snapshot of the Ub ligation step on a specific target residue of TRIM211-91 as an auto-ubiquitinated pseudo-substrate at high concentration. Increased structural and functional understanding of the TRIM mediated ubiquitination will aid development ofnovel therapeutic approaches in the entire TRIM family ofproteins.

  • 68.
    Anandapadmanaban, Madhanagopal
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Pilstål, Robert
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Andrésen, Cecilia
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Trewhella, Jill
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. University of Sydney, Australia.
    Moche, Martin
    Karolinska Institute, Sweden.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression2016Inngår i: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 24, nr 8, s. 1311-1321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 angstrom) presented here is closely similar to wildtype MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members.

  • 69.
    Ananthakrishnan, Gopal
    et al.
    Centre for Speech Technology, KTH, Stockholm, Sweden.
    Eklund, Robert
    Linköpings universitet, Institutionen för datavetenskap, NLPLAB - Laboratoriet för databehandling av naturligt språk. Linköpings universitet, Tekniska högskolan.
    Peters, Gustav
    Forschungsinstitut Alexander Koenig, Bonn, Germany.
    Mabiza, Evans
    Antelope Park, Gweru, Zimbabwe.
    An acoustic analysis of lion roars. II: Vocal tract characteristics2011Inngår i: Proceedings from Fonetik 2011, Quarterly Progress and Status Report TMH-QPSR, Volume 51, 2011, 2011, s. 5-8Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    This paper makes the first attempt to perform an acoustic-to-articulatory inversion of a lion (Panthera leo) roar. The main problems that one encounters in attempting this, is the fact that little is known about the dimensions of the vocal tract, other than a general range of vocal tract lengths. Precious little is also known about the articulation strategies that are adopted by the lion while roaring. The approach used here is to iterate between possible values of vocal tract lengths and vocal tract configurations. Since there seems to be a distinct articulatory changes during the process of a roar, we find a smooth path that minimizes the error function between a recorded roar and the simulated roar using a variable length articulatory model.

  • 70.
    Anderson, Claes
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Habituation towards environmental enrichment in captive bears and its effect on stereotypic behaviours.2008Independent thesis Advanced level (degree of Master), 40 poäng / 60 hpOppgave
    Abstract [en]

    The benefits gained by the presentation of environmental enrichment (EE) to captive animals are widely recognized. Few studies have, however, studied how to maximize the effect of EE. Repeated presentations of EE may cause a reduced interest towards the EE device, called habituation. To study the effect of habituation towards EE, behavioural data from 14 captive Sloth bears (Melursus ursinus) were collected during two different EE treatments. In treatment one, honey logs were presented for five consecutive days (ConsEE). In treatment two, the logs were presented every alternative day for five days (AltEE). The different treatments both showed a significant effect on responsiveness toward the EE, however, leaving gap days inbetween presentations in AltEE showed no reliable reduction in habituation. Both treatments significantly reduced stereotypies, however, only ConsEE reduced levels of stereotypies long term. Explorative behaviours, which are the most prominent behaviours in the wild, increased during both treatments. This is consistent with previous findings (Fischbacher & Schmid 1999, Grandia et al. 2001) that EE increases natural behaviours, which has been desribed as an indication of improved welfare (Carlstead et al. 1991 etc.). Other behavioural categories such as social and passiva behaviours were unaffected by the EE presentations. THe results show that it is possible to increase the effectiveness of EE by simple means in order to ensure animal welfare.

  • 71.
    Anderson, Claes
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Zoologi. Linköpings universitet, Tekniska högskolan.
    Shanmugam, Attur
    Wildlife SOS, Bannerghatta Bear Rescue Centre, Bannerghatta Biological Park, Bannerghatta, Bangalore, Karnataka, India.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Zoologi. Linköpings universitet, Tekniska högskolan.
    Habituation to Environmental Enrichment in Captive Sloth Bears - Effect on Stereotypies2010Inngår i: Zoo Biology, ISSN 0733-3188, E-ISSN 1098-2361, Vol. 28, nr 6, s. 1-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The benefits to captive animals of environmental enrichment (EE) are widely recognized. Few studies have, however, studied how to maximise the effect of EE. One issue with EE programs seems to be habituation to the enrichment device. To study the effect of habituation to EE, 14 captive sloth bears (Melursus ursinus) were subjected to two different EE treatments. Treatment one presented EE (logs with honey containing holes) for five consecutive days, whereas treatment two presented EE on intermittent days for five days. Intermittent presentations tended to reduce habituation toward the EE. Both consecutive and intermittent presentations significantly reduced stereotypies; however, the consecutive presentations had a longer-lasting effect. Explorative behaviors increased in both treatments, consistent with earlier findings that EE increase levels of natural behaviors. Other behaviors were unaffected by the EE presentations. The results show that intermittent presentation of EE objects may secure the interest of the animals, but continuous access to enrichment may be more efficient in reducing stereotypies in the long run.

  • 72.
    Anderson, Judy E.
    et al.
    Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada; Manitoba Institute of Child's Health (MICH), University of Manitoba, Winnipeg, Canada.
    Hansen, Lise Lotte
    Institute of Human Genetics, University of Aarhus, Denmark.
    Mooren, Frank C.
    Department of Sports Medicine, Institute of Sport Sciences, University Giessen, Germany.
    Post, Markus
    Department of Sports Medicine, Institute of Sport Sciences, University Giessen, Germany.
    Hug, Hubert
    DSM Nutritional Products Ltd, Research & Development, Kaiseraugst, Switzerland.
    Zuse, Anne
    Manitoba Institute of Cell Biology (MICB), CancerCare Manitoba, 675 McDermot Ave. Rm. ON6010, Winnipeg, Man. R3E 0V9, Canada.
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Methods and biomarkers for the diagnosis and prognosis of cancer and other diseases: Towards personalized medicine2006Inngår i: Drug resistance updates, ISSN 1368-7646, E-ISSN 1532-2084, Vol. 9, nr 4-5, s. 198-210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rapid development of new diagnostic procedures, the mapping of the human genome, progress in mapping genetic polymorphisms, and recent advances in nucleic acid- and protein chip technologies are driving the development of personalized therapies. This breakthrough in medicine is expected to be achieved largely due to the implementation of "lab-on-the-chip" technology capable of performing hundreds, even thousands of biochemical, cellular and genetic tests on a single sample of blood or other body fluid. Focusing on a few disease-specific examples, this review discusses selected technologies and their combinations likely to be incorporated in the "lab-on-the-chip" and to provide rapid and versatile information about specific diseases entities. Focusing on breast cancer and after an overview of single-nucleofide polymorphism (SNP)-screening methodologies, we discuss the diagnostic and prognostic importance of SNPs. Next, using Duchenne muscular dystrophy (DMD) as an example, we provide a brief overview of powerful and innovative integration of traditional immuno-histochemistry techniques with advanced biophysical methods such as NMR-spectroscopy or Fourier-transformed infrared (FT-IR) spectroscopy. A brief overview of the challenges and opportunities provided by protein and aptamer microarrays follows. We conclude by highlighting novel and promising biochemical markers for the development of personalized treatment of cancer and other diseases: serum cytochrome c, cytokeratin-18 and -19 and their proteolytic fragments for the detection and quantitation of malignant tumor mass, tumor cell turn-over, inflammatory processes during hepatitis and Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis and apoptotic/necrotic cancer cell death. (c) 2006 Elsevier Ltd. All rights reserved.

  • 73.
    Anderson, Malin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ekologi.
    Dynamics of phosphorus transport and retention in a wetland receiving drainage water from agricultural clay soils2011Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    A constructed wetland (0.08 ha) receiving drainage water from a small agricultural catchment (22 ha) with clay soil, was investigated with respect to phosphorus dynamics and retention. The aim was to evaluate the function of the wetland with respect to phosphorus retention, and relate that to gross sedimentation as measured with sediment traps. Hydraulic load and phosphorus retention were estimated for 2003-2010 based on monitoring data. Furthermore, water quality dynamics was studied during three intensive sampling periods of 3-5 days during 2010. For each period, phosphorus retention was calculated and the relationship between flow and phosphorus concentrations analysed. Additionally, the gross sedimentation rate was estimated using sediment traps, and the phosphorus, carbon and nitrogen content analysed. The results suggested that there was no net retention of phosphorus during 2003-2010, except for 04/05. During the intensive sampling periods, release of phosphorus from the wetland mainly occurred during high flow. Sediment analyses showed that settling of inflow particles mostly occurred in the inlet pond, while the sediment found in a shallow vegetated area and outlet pond likely originated from internal processes rather than from the catchment. In fact, the gross sedimentation of phosphorus during April-July and July-August, respectively, exceeded the measured phosphorus inflow. The results showed that short periods with rapid flow increases were crucial for the wetlands function and thus high frequency sampling must be done during these periods. Furthermore, it seems that the particles lost from the catchment during high flows are too small to settle in the wetland.

  • 74.
    Andersson, Anton
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Berg, Astrid
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Rådkvist, Emil
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Wennberg, Sara
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    von Zweigbergk, Jacob
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Sojans roll i världen2019Independent thesis Basic level (degree of Bachelor), 12 poäng / 18 hpOppgave
    Abstract [en]

    The soybean has become one of the world's largest agricultural commodities, with growth in soybean production being driven by two prime demands, animal feed and food products. The purpose of this report is to analyze the role of the soybean in the world and study its consumption in order to make a projection of future demand. The report is based on literature and data from previous studies and public databases, and the main way of analyzing the role of soybean production is through valuation of the ecosystem services lost in conversion to cropland. Argentina, Brazil and the USA are the main producers of soybean, and as such they were the focus of the production segment. In all these countries the conversion rate of natural ecosystems was found to be high, with losses of ecosystem services as a result. Demand showed steady growth and the projection indicated that it would continue to grow, creating the question of where to convert natural habitat to new cropland. The result shows there is a lack of such suitable land, and hence a reduced demand is the only viable solution. As animal feed is the main driver of demand, the conclusion is that the main way of reducing demand is to change our eating habits and reducing animal products in our diets. 

  • 75.
    Andersson, Elin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska högskolan. IFM.
    Dogs´understanding of human pointing gestures2014Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    To investigate the ability for animals to understand human communication signals and the communication between animals and humans, scientists often investigate the understanding of human gestural cues. Dogs (Canis lupus familiaris) which have a long history of co-evolution with humans have been shown to make good use of human gestural cues. In the present study I investigated whether dogs in general understand a human pointing gesture and if there are differences between sex, age or breeds. In total 46 dogs of different breeds participated in the study. The study was carried out in a dog center in Linköping, Hundens och djurens beteendecenter. To test if dogs understand human pointing gestures, a two-way object choice test were used, where an experimenter pointed at a baited bowl at a distance of three meter from the dog. The results showed that dogs in general can understand human pointing gestures. However, no significant differences were found for sex, age or breeds. As a conclusion, I found that dogs in general can understand human pointing gestures, but sex, age or breed did not affect the ability.

  • 76.
    Andersson, Emelie
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Social environment influences impulsivity in red junglefowl (Gallus gallus) chicks2019Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    Cognition (i.e. how individuals perceive, process and react to environmental cues) is fundamental to all animals’ life. Despite this, what explains variation in cognitive abilities is still mainly unclear. Environment is assumed to influences cognitive variation, but the mechanisms for this are still unknown. According to the social intelligence hypothesis, living in a group with a rich social environment, generate challenges that can enhance cognitive abilities. Impulsivity (to not be able to inhibit impulses), one aspect of cognition, may be influenced by the social environment, however this has not yet been experimentally tested. Impulsivity can complicate life, both for humans and animals. In humans, high levels of impulsivity and lack of self-control are associated with addictions and psychiatric disorders, thus is considered to be maladaptive. In animals, impulsivity correlates with stereotypies. To improve our understanding of impulsivity, I experimentally investigated how early social environment affects individual variation in impulsivity. To test this, red junglefowl chicks were used because their group living nature, and our accumulated knowledge on their cognition and behaviour. To manipulate the social environment, chicks either grew up in larger groups (with 17 individuals) or smaller groups (with 7 individuals). During the chicks’ first five weeks of life, three aspects of impulsivity were tested; impulsive action, persistence (in a detour reaching test) and routine formation (in a reversal learning test). Chicks that grew up in larger groups tended to perform less impulsive actions, while social environment did not explain variation in persistence. Chicks from larger groups had less strong routine formation compared to chicks raised in smaller groups. This partially supports the social intelligence hypothesis, and suggest that early social life can affect cognitive traits and explain individual variation in such.

  • 77.
    Andersson, Johanna
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Lärande, Estetik, Naturvetenskap (LEN). Linköpings universitet, Utbildningsvetenskap.
    Tibell, Lena
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Medie- och Informationsteknik. Linköpings universitet, Utbildningsvetenskap.
    Exploring childrens' views of what's inside the body2012Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The importance of living a healthy life in an everyday context is promoted in schools and preschools. The discussion often focuses on what food is healthy, and that one should eat enough but not too much. The connection between food and beverages and their role in the body is seldom discussed. Students’ ideas about how the human body functions have been investigated in several studies but few have focused on young children. In this study, we investigate young children’s conceptions related to this topic and how their ideas develop. Seventy-nine pre- and primary school children, aged 4-11, participated in individual focus interviews wherein the children were asked to draw and explain their understanding. Our results confirm several findings observed by other workers. However, in contrast with earlier studies, 10 of seventeen 4-5 year-old children indicated the stomach, and more than half of those children described how food can be utilized in the body to extract energy. Furthermore, the brain was among the most commonly mentioned organs cross all age groups. Interestingly, the level of expertise varied and did not covariate with age. For example, five of eight of the 4 year-old children draw 5-8 organs, while a single 10 year-old child could only mention three. Similarly, two of thirteen 7-year old children provided an almost completely correct description of the digestive tract and its function, while most of the older children expressed a much less developed understanding. The results reflect the wide range of different conceptual ideas that teachers confront in a day-to-day classroom context.

  • 78.
    Andersson, Johanna
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Lärande, Estetik, Naturvetenskap (LEN). Linköpings universitet, Utbildningsvetenskap.
    Tibell, Lena A.E.
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Medie- och Informationsteknik. Linköpings universitet, Utbildningsvetenskap.
    Children's reasoning and representations about living and non-living things2013Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Understanding of the concept ‘life’ and what characterise ‘living things’ is important as a foundation for learning in biology. In a more general view, this understanding can make children develop awareness, respect and responsibility for life as members of a society and in decision making for sustainable development. The present pilot study aim to investigate 5-6 year old pre-school children’s reasoning and representations about living and nonliving things. In cognitive developmental research, the concept of life is well investigated but, questions still remain regarding how children reason around and represent these concepts. Previous research has found that children have difficulties in including plants as living things. Moreover, it is found that young children include e.g. the sun, clouds and rocks as living things. The methods that have been used are often quantitative and use picture-cards with different objects for the children to categorize. In the present pilot study a modified methodology was applied. Children’s drawings of what they consider as living and non-living were collected and picture-cards were used as point of departure for reasoning. In interviews the children were encouraged to explain and express their ideas. The drawings and the cards mainly worked as a meaning making tool for the children. Results from the study will be presented and discussed. 

  • 79.
    Andersson, Jonathan
    et al.
    Linköpings universitet, Matematiska institutionen, Matematik och tillämpad matematik. Linköpings universitet, Tekniska fakulteten.
    Kozlov, Vladimir
    Linköpings universitet, Matematiska institutionen, Matematik och tillämpad matematik. Linköpings universitet, Tekniska fakulteten.
    Radosavljevic, Sonja
    Stockholm Resilience Centre, Stockholm University, Stockholm, Sweden.
    Tkachev, Vladimir
    Linköpings universitet, Matematiska institutionen, Matematik och tillämpad matematik. Linköpings universitet, Tekniska fakulteten.
    Wennergren, Uno
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Biologi. Linköpings universitet, Tekniska fakulteten.
    Density-Dependent Feedback in Age-Structured Populations2019Inngår i: Journal of Mathematical Sciences, ISSN 1072-3374, E-ISSN 1573-8795, Vol. 242, nr 1, s. 2-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The population size has far-reaching effects on the fitness of the population, that, in its turn influences the population extinction or persistence. Understanding the density- and age-dependent factors will facilitate more accurate predictions about the population dynamics and its asymptotic behaviour. In this paper, we develop a rigourous mathematical analysis to study positive and negative effects of increased population density in the classical nonlinear age-structured population model introduced by Gurtin \& MacCamy in the late 1970s. One of our main results expresses the global stability of the system in terms of the newborn function only. We also derive the existence of a threshold population size implying the population extinction, which is well-known in population dynamics as an Allee effect.

  • 80.
    Andersson, Magnus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ekologi.
    Selective predation by perch (Perca fluviatilis) on a freshwater isopod, in two macrophyte substrates.2010Independent thesis Advanced level (degree of Master (Two Years)), 40 poäng / 60 hpOppgave
    Abstract [en]

    Recent studies show that populations of the freshwater isopod Asellus aquaticus L. can rapidly become locally differentiated when submerged stonewort (Chara spp.) vegetation expands in lakes. In the novel Chara habitat, isopods become lighter pigmented and smaller than in the ancestral reed stands. In this study, I used laboratory experiments to investigate if selective predation by fish could be a possible explanation for these phenotypic changes. Predation from fish is generally considered to be a strong selective force on macroinvertebrate traits. In the first experiment I measured perch (Perca fluviatilis L.) handling time for three size classes of Asellus to see which size of those that would be the most profitable to feed upon. No difference in handling time was detected between prey sizes, hence the largest size would be the most beneficial to feed upon. In a second experiment I let perch feed on a mixture of Asellus phenotypes in aquaria manipulated to mimic the substrates in either the Chara or the reed habitats. Remaining isopods were significantly smaller and lighter pigmented in the fish aquaria than in the controls, showing that the perch preferred to feed on large and dark individuals. In the Chara habitat, selection on isopod pigmentation was according to what could be expected from background matching, but in the reed habitat selection was quite the opposite. These results support the hypothesis that predation from fish is a strong selective force behind the rapid local adaptation seen in Asellus populations in the novel Chara habitat.

  • 81.
    Andersson, Marie
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Elucidation of the product synthesis of the sesquiterpene synthase Cop6 isolated from Coprinus cinereus2009Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Mushrooms are believed to have a great potential for production of bioactive metabolites e. g. terpenes, a group of interesting compounds with diverse chemical properties such as antitumour and antibacterial activity. Cop6 is a terpene cyclase isolated from the mushroom Coprinus cinereus that catalyzes the cyclization of farnesyl diphosphate (FPP) to mainly α-cuprenene. In this study gas chromatography combined with mass spectroscopy (GC-MS) is used to analyze the product profile of Cop6 mutants created by PCR based site directed mutagenesis. The goal is to produce trichodiene, the parent hydrocarbon in the biosynthesis of trichothecene antibiotics and mycotoxins. Valine instead of tyrosine in amino acid position 195 resulted in cyclisation of (E)-β-Farnesene and (3Z,6E)-α-Farnesene besides the products of the wild type enzyme. Another mutant with aspartic acid instead of asparagine in position 224 resulted in the synthesis of β-Bisabolene except for α-cuprenene and methionine in position 74 instead of isoleucine killed the activity of the cyclase. Furthermore, an attempt to saturation of position 98 was made, resulting in four mutants. Two of them essentially killed the activity of the cyclase whereas two had minor effect of the product profile compared to the wild type. 

  • 82.
    Andersson, Marie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ekologi.
    Oak (Quercus robur L.) mortality in south-eastern Sweden: influence of weather and environmental variables2009Independent thesis Advanced level (degree of Master (Two Years)), 40 poäng / 60 hpOppgave
    Abstract [en]

    The complex interplay between biotic and abiotic factors, believed to be responsible for several oak declines in European oak stands during the last three decades, remains poorly understood. Hence, this study aims at clarifying the temporal process of oak declines, as well as identifying individual tree and environmental variables that increase the risk of oak mortality. The study was performed in one of the few areas in northern Europe still holding high densities of old oaks (Quercus robur L.). Cross dating revealed that most trees had died during the last decade. Averaged chronologies and multiple chronological clustering suggested that the onset of the oak decline happened in 1992, when a severe drought took place. Two of the sites showed a rather short time period of heavily reduced growth prior to death, most likely caused by an insect defoliation in combination with a mildew infection of the replacement shoots. Environmental variables presented a rather weak influence on oak mortality. The results support the idea of attributing oak mortality to a combination of long- and short-term stresses, and emphasize the importance of including present as well as past factors when analysing the causes of oak declines.

  • 83.
    Andersson, Natasja
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Personlighetsvariationer hos mjölkkor2010Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Syftet med denna studie var att undersöka om det fanns olika personlighetstyper hos mjölkkor av raserna SRB och SLB och om dessa personlighetstyper skilde sig mellan ras, ålder och vilken sida djuren stått på i lösdriften. Korna observerades i tre olika testmiljöer för att se huruvida konsistenta de var i deras beteenden: ostörda i lösdriften, vid mjölkning och med ett främmande objekt i lösdriften. Beteenden som studerades var normala beteenden, sociala beteenden, tramp och sparkningar vid mjölkning och interaktioner med det främmande objektet. Tolv beteendevariabler användes i en PCA (principal component analysis) och visade två komponenter som tillsammans kunde förklara 51,2 % av den totala variansen. Den första komponenten speglade aggression och extraversion, som ingår i medgörlighet och extraversion i den mänskliga femfaktorsmodellen. Den andra komponenten speglade ett mer introvert beteende och rädsla, som går under extraversion och neuroticism i samma modell. Oberoende T-test visade inga signifikanta skillnader mellan någon av komponenterna och ras eller sida i lösdriften p>0,05, däremot en tendens till skillnad mellan den första komponenten och ålder, där den äldre gruppen individer visade tydligare personlighetsdrag p<0.1. Tidigare studier har visat att personlighetsdimensioner som medgörlighet, neuroticism och extraversion ofta förekommer bland flera arter. Då olika personligheter hanterar stressfulla situationer på olika sätt, är detta ämne av stor vikt när det gäller förbättrandet av djurens välfärd.

  • 84.
    Andersson, Rebecca
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi.
    An Evaluation of Two Presumptive Blood Tests and Three Methods to Visualise Blood2017Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    The aim of this study was to validate the two presumptive blood tests LMG, LCV and the three visualising blood methods Bluestar Forensics, Lumiscene and the Ruhoff method. The methods’ sensitivity, durability, matrices effects, false positive results and the methods effect on subsequent DNA analysis were studied. DNA analyses were also performed to assess the detection limit of the forensic DNA analysis. Drops of diluted blood were applied on different absorptive matrices and the sensitivity was investigated. The solutions were also placed under different conditions to investigate the durability of the solutions. The solutions were applied upon panels using different chemicals and materials and the false positive results were studied. The DNA analyses were performed by diluting the blood with Bluestar Forensics, the hydrogen peroxide method, the Ruhoff method and deionised water. The study showed that the LMG with a 3 % H2O2 concentration performs the best and it is suited for practical casework. The positive results of LMG was easier to interpret than those of LCV, this is probably due to the fixative agent of the used LCV solution. Bluestar Forensics and Lumiscene did perform similar on the different matrices tested, but the Lumiscene solution had a slightly higher durability. The results strongly indicate that the Ruhoff method can be used without luminol, hence only as a hydrogen peroxide solution (the hydrogen peroxide method). All three visualising blood methods decreases chances of retrieving a positive DNA profile, however the visualising blood methods could be used if the blood cannot be found in any other way. A DNA profile was obtained from the one blood sample analysed at dilution of 1:256 in deionized water.

  • 85.
    Anderzén, Emma
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Beror förekomsten av sjöfågel i anlagda våtmarker på våtmarkens ålder och area?2011Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [sv]

    Av naturvårdsskäl är det viktigt att förstå vilken betydelse area och ålder på anlagda våtmarker har för artsammansättningen av sjöfåglar. I Linköpings kommun har man sedan 2004 anlagt ett flertal våtmarker och dessa har lockat bland annat den rödlistade arten svarthakedopping, Podiceps auritus, i stor mängd. Våtmarker är viktiga för fågellivet av många olika anledningar. Bland annat kan fåglarna söka skydd mot predatorer, häcka där eller rasta på sin väg mot häckningsplatser. Tidigare studier har bland annat visat att det finns fler fåglar i större våtmarker och att våtmarkens ålder spelar roll för vilka fågelarter som går att finna där. Genom räkning av antal fågelindivider och vilka olika arter som finns i de olika våtmarkerna kunde vi se att både ålder och storlek på våtmarken hade betydelse för vilka fåglar som utnyttjade dessa. Ju större våtmark desto fler fågelindivider och olika arter fanns det där. Det visar sig också att fågellivet gynnades då det fanns flera våtmarker av olika storlek och ålder i området. Vi kunde även se att svarthakedoppingens täthet var störst i lite mindre våtmarker och ökade signifikant med ökande antal skrattmåsar i våtmarken.

  • 86.
    Andrésen, Cecilia
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Niklasson, Markus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Cassman Eklöf, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Biophysical characterization of the calmodulin-like domain of Plasmodium falciparum calcium dependent protein kinase 32017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, artikkel-id e0181721Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Calcium dependent protein kinases are unique to plants and certain parasites and comprise an N-terminal segment and a kinase domain that is regulated by a C-terminal calcium binding domain. Since the proteins are not found in man they are potential drug targets. We have characterized the calcium binding lobes of the regulatory domain of calcium dependent protein kinase 3 from the malaria parasite Plasmodium falciparum. Despite being structurally similar, the two lobes differ in several other regards. While the monomeric N-terminal lobe changes its structure in response to calcium binding and shows global dynamics on the sub-millisecond time-scale both in its apo and calcium bound states, the C-terminal lobe could not be prepared calcium-free and forms dimers in solution. If our results can be generalized to the full-length protein, they suggest that the C-terminal lobe is calcium bound even at basal levels and that activation is caused by the structural reorganization associated with binding of a single calcium ion to the N-terminal lobe.

  • 87.
    Anel-López, Luis
    et al.
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Alvarez-Rodríguez, Manuel
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    García-Álvarez, Olga
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Maroto-Morales, Alejandro
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Garde, J Julián
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Martínez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Reduced glutathione and Trolox (vitamin E) as extender supplements in cryopreservation of red deer epididymal spermatozoa2012Inngår i: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 135, nr 1-4, s. 37-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of assisted reproductive techniques in cervids is increasing as the commercial use of these species increase. We have tested the suitability of the antioxidants Trolox and reduced glutathione (GSH) for freezing red deer epididymal spermatozoa, aiming at improving post-thawing quality. Samples from 19 stags were frozen in a TES-Tris-fructose extender (20% egg yolk, 8% glycerol), with 1 or 5 mM of antioxidant. Motility (CASA), lipoperoxidation (malondialdehyde -MDA- production), membrane status, mitochondrial activity, acrosomal status (flow cytometry) and chromatin status (SCSA: %DFI and %HDS; flow cytometry) were assessed after thawing and after 6 h at 39°C. There were few differences between treatments after thawing, with Trolox reducing MDA production in a dose-response manner. After the incubation, sperm quality decreased and %DFI increased moderately, with no change for MDA. GSH improved motility, kinematic parameters and mitochondrial status, with a slight increase in %HDS. GSH 5 mM also increased moderately MDA production and %DFI, possibly due to enhanced metabolic activity and reducing power. Trolox maintained MDA low, but was detrimental to sperm quality. Trolox might not be appropriate for the cryopreservation of red deer epididymal spermatozoa, at least at the millimolar range. GSH results are promising, especially regarding motility improvement after the post-thawing incubation, and should be selected for future fertility trials.

  • 88.
    Ansell, Ricky
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten. Nationellt forensiskt center, Linköping, Sverige.
    Dna-möte på NFC2015Inngår i: KriminalteknikArtikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 89.
    Ansell, Ricky
    Statens kriminaltekniska laboratorium, Linköping.
    Dna-spår betydelsefulla i sexualbrottsärenden2014Inngår i: Kriminalteknik, ISSN 1653-6169, nr 3, s. 16-17Artikkel i tidsskrift (Annet vitenskapelig)
  • 90.
    Ansell, Ricky
    Nationellt forensiskt center - NFC, Linköping, Sverige.
    Forensisk dna-kongress i Krakow – ISFG 20152015Inngår i: Kriminalteknik, ISSN 1653-6169Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 91.
    Ansell, Ricky
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska högskolan.
    Pilotstudie om forensiska uppslag2014Inngår i: KriminalteknikArtikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 92.
    Ansell, Ricky
    et al.
    Swedish National Forensic Centre, Linköping, Sweden.
    Allen, Marie
    Molekylär patologi och rättsgenetik, Uppsala universitet.
    DNA-analyser inom brottsbekämpningen2016Inngår i: Skurk, sjuk eller släkt?: vem ska ha ditt DNA? / [ed] Eva Regårdh, Sofie Pehrssoon, Stockholm: Stiftelsen för strategisk forskning , 2016, s. 18-27Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [sv]

    Idag räcker det med DNA från enstaka celler för att kunna få fram en DNA-profil som kan jämföras med per-soner eller andra DNA-spår. En DNA-träff mot ett biologiskt spår kan utgöra en mycket stark bevisning och vara avgörande för en fällande dom. DNA-teknik gör det möjligt att analysera och ta fram en DNA-profil för de allra flesta typer av humana biologiska spår som avsatts i samband med brott, såsom blod, sperma, vaginalsekret, saliv, hår och ”kontaktspår”. Teknikerna har med åren utvecklats och förfinats. På senare år har också det internationella utbytet av DNA-profiler ökat samtidigt som fortsatt teknik- och metodutveckling banar väg för fördjupade analy-ser som kan bidra till att klara upp brott. Det kan handla om att utifrån DNA-spår ringa in ungefärlig ålder, ursprung, hårfärg, ögonfärg och kroppsstorlek på en misstänkt gärningsman

  • 93.
    Ansell, Ricky
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten. Polismyndigheten - Nationellt Forensiskt Centrum.
    Nordgaard, Anders
    Linköpings universitet, Institutionen för datavetenskap, Statistik. Linköpings universitet, Filosofiska fakulteten. Polismyndigheten - Nationellt Forensiskt Centrum.
    Hedell, Ronny
    Polismyndigheten - Nationellt Forensiskt Centrum.
    Interpretation of DNA Evidence: Implications of Thresholds Used in the Forensic Laboratory2014Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Evaluation of forensic evidence is a process lined with decisions and balancing, not infrequently with a substantial deal of subjectivity. Already at the crime scene a lot of decisions have to be made about search strategies, the amount of evidence and traces recovered, later prioritised and sent further to the forensic laboratory etc. Within the laboratory there must be several criteria (often in terms of numbers) on how much and what parts of the material should be analysed. In addition there is often a restricted timeframe for delivery of a statement to the commissioner, which in reality might influence on the work done. The path of DNA evidence from the recovery of a trace at the crime scene to the interpretation and evaluation made in court involves several decisions based on cut-offs of different kinds. These include quality assurance thresholds like limits of detection and quantitation, but also less strictly defined thresholds like upper limits on prevalence of alleles not observed in DNA databases. In a verbal scale of conclusions there are lower limits on likelihood ratios for DNA evidence above which the evidence can be said to strongly support, very strongly support, etc. a proposition about the source of the evidence. Such thresholds may be arbitrarily chosen or based on logical reasoning with probabilities. However, likelihood ratios for DNA evidence depend strongly on the population of potential donors, and this may not be understood among the end-users of such a verbal scale. Even apparently strong DNA evidence against a suspect may be reported on each side of a threshold in the scale depending on whether a close relative is part of the donor population or not. In this presentation we review the use of thresholds and cut-offs in DNA analysis and interpretation and investigate the sensitivity of the final evaluation to how such rules are defined. In particular we show what are the effects of cut-offs when multiple propositions about alternative sources of a trace cannot be avoided, e.g. when there are close relatives to the suspect with high propensities to have left the trace. Moreover, we discuss the possibility of including costs (in terms of time or money) for a decision-theoretic approach in which expected values of information could be analysed.

  • 94.
    Ansell, Ricky
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska högskolan.
    Widén, Christina
    Statens kriminaltekniska laboratorium.
    Ny lagstiftning för DNA elimineringsbas i Sverige2014Inngår i: Kriminalteknik, Vol. 4, s. 28-30Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 95.
    Appelgren, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Segelmark, Mårten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis2018Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, artikkel-id 2242Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and Bl-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naive patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity.

  • 96.
    Appelqvist, Hanna
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Stranius, Kati
    University of Gothenburg, Sweden.
    Börjesson, Karl
    University of Gothenburg, Sweden.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Dyrager, Christine
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Specific Imaging of Intracellular Lipid Droplets Using a Benzothiadiazole Derivative with Solvatochromic Properties2017Inngår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 28, nr 5, s. 1363-1370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Altered lipid metabolism and extensive lipid storage in cells have been associated with various medical disorders, including cancer. The development of fluorescent probes that specifically accumulate in lipid deposits is therefore of great interest in order to study pathological processes that are linked to dysregulated lipogenesis. In the present study, we present a small fluorescent benzothiadiazole dye that specifically stains lipid droplets in living and fixated cells. The photophysical characterization of the probe revealed strong solvatochromic behavior, large Stokes shifts, and high fluorescent quantum yields in hydrophobic solvents. In addition, the fluorophore exhibits a nontoxic profile and a high signal-to-noise ratio in cells (i.e., lipid droplets vs cytosol), which make it an excellent candidate for studying lipid biology using confocal fluorescent microscopy.

  • 97.
    Aravantinou, Meropi
    et al.
    Populat Council, NY 10021 USA.
    Frank, Ines
    Populat Council, NY 10021 USA.
    Hallor, Magnus
    Linköpings universitet. Populat Council, NY 10021 USA.
    Singer, Rachel
    Populat Council, NY 10021 USA.
    Tharinger, Hugo
    Populat Council, NY 10021 USA.
    Kenney, Jessica
    Populat Council, NY 10021 USA.
    Gettie, Agegnehu
    Rockefeller University, NY 10021 USA.
    Grasperge, Brooke
    Tulane University, LA USA.
    Blanchard, James
    Tulane University, LA USA.
    Salazar, Andres
    Oncovir Inc, DC USA.
    Piatak, Michael Jr.
    Leidos Biomed Research Inc, MD USA.
    Lifson, Jeffrey D.
    Leidos Biomed Research Inc, MD USA.
    Robbiani, Melissa
    Populat Council, NY 10021 USA.
    Derby, Nina
    Populat Council, NY 10021 USA.
    PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 9, artikkel-id e0161730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239 Delta Nef (SIV Delta Nef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of alpha(4)beta(7) and CD169, and induced type IIFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro-and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIV Delta Nef-infected animals, SIV Delta Nef viremia was higher, in line with the importance of DC and T cell activation in SIV Delta Nef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity.

  • 98.
    Arja, Katriann
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Elgland, Mathias
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Synthesis and Characterization of Oligothiophene-Porphyrin-Based Molecules That Can Be Utilized for Optical Assignment of Aggregated Amyloid-beta Morphotypes2018Inngår i: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 6, artikkel-id 391Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular tools for fluorescent imaging of protein aggregates are essential for understanding the significance of these pathological hallmarks in proteopathic neurodegenerative diseases, such as Alzheimers disease. Here, we report the synthesis of a series of oligothiophene porphyrin hybrids, OTPHs, and the evaluation of these dyes for fluorescent imaging of beta-amyloid aggregates in tissue sections from a transgenic mouse model with Alzheimers disease pathology. The OTPHs proved to be successful for spectral and lifetime imaging assessment of protein deposits and our findings confirm that the enhanced spectral range and distinct lifetime diversity of these novel tools allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye. In addition, the chemical identity of the porphyrin moiety, as well as the spacing between the two optical active moieties, influenced the OTPHs performance for fluorescent assignment of the protein deposits. We foresee that our findings will aid in the chemical design of dyes that can be utilized as optical tools for studying the polymorphic nature of protein aggregates associated with proteopathic neurodegenerative diseases.

  • 99.
    Arnqvist, Göran
    et al.
    Department of Ecology and Environmental Science, Animal Ecology, University of Umeå, Umeå, Sweden.
    Edvardsson, Martin
    Department of Ecology and Environmental Science, Animal Ecology, University of Umeå, Umeå, Sweden.
    Friberg, Urban
    Department of Ecology and Environmental Science, Animal Ecology, University of Umeå, Umeå, Sweden.
    Nilsson, Tina
    Department of Ecology and Environmental Science, Animal Ecology, University of Umeå, Umeå, Sweden.
    Sexual conflict promotes speciation in insects.2000Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, nr 19, s. 10460-10464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Speciation rates among extant lineages of organisms vary extensively, but our understanding of the causes of this variation and, therefore, the processes of speciation is still remarkably incomplete. Both theoretical and empirical studies have indicated that sexual selection is important in speciation, but earlier discussions have focused almost exclusively on the potential role of female mate choice. Recent findings of postmating reproductive conflicts of interest between the sexes suggest a quite different route to speciation. Such conflicts may lead to perpetual antagonistic coevolution between males and females and may thus generate rapid evolutionary divergence of traits involved in reproduction. Here, we assess this hypothesis by contrasting pairs of related groups of insect species differing in the opportunity for postmating sexual conflict. Groups where females mate with many males exhibited speciation rates four times as high as in related groups where females mate only once. Our results not only highlight the general importance of postmating sexual selection in speciation, but also support the recent suggestion that sexual conflict is a key engine of speciation.

  • 100.
    Aronsson, Christopher
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.

    The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.

    By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.

    The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery

    .

    Delarbeid
    1. Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
    Åpne denne publikasjonen i ny fane eller vindu >>Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
    Vise andre…
    2015 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, nr 14063Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide-based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials.

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    NATURE PUBLISHING GROUP, 2015
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-121739 (URN)10.1038/srep14063 (DOI)000361177400001 ()26370878 (PubMedID)
    Merknad

    Funding Agencies|Swedish Research Council (VR); Swedish Foundation for Strategic Research (SSF)

    Tilgjengelig fra: 2015-10-06 Laget: 2015-10-05 Sist oppdatert: 2019-01-22
    2. Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
    Åpne denne publikasjonen i ny fane eller vindu >>Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting
    2016 (engelsk)Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, nr 6, s. 2260-2267Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties. Tailoring these properties demands exquisite control over the supramolecular peptides with different affinities for dimerization. Four different mechanical properties of hydrogels using de novo designed coiled coil interactions involved. Here we show that it is possible to control the nonorthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from mu M to pM, were conjugated to star-shaped 4-arm poly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG peptide conjugates assemble into PEG peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular, and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of nonpegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.

    sted, utgiver, år, opplag, sider
    AMER CHEMICAL SOC, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-130135 (URN)10.1021/acs.biomac.6b00528 (DOI)000377924800038 ()27219681 (PubMedID)
    Merknad

    Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]

    Tilgjengelig fra: 2016-07-12 Laget: 2016-07-11 Sist oppdatert: 2019-01-22
    3. Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
    Åpne denne publikasjonen i ny fane eller vindu >>Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release
    2016 (engelsk)Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 49, nr 18, s. 6997-7003Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We demonstrate a novel route for hierarchical self-assembly of sub-micrometer-sized peptide superstructures that respond to subtle changes in Zn2+ concentration. The self-assembly process is triggered by a specific folding-dependent coordination of Zn2+ by a de novo designed nonlinear helix-loop-helix peptide, resulting in a propagating fiber formation and formation of spherical superstructures. The superstructures further form larger assemblies that can be completely disassembled upon removal of Zn2+ or degradation of the nonlinear peptide. This flexible and reversible assembly strategy of the superstructures enables facile encapsulation of nanoparticles and drugs that can be released by means of different stimuli.

    sted, utgiver, år, opplag, sider
    AMER CHEMICAL SOC, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-132215 (URN)10.1021/acs.macromol.6b01724 (DOI)000384399100030 ()
    Merknad

    Funding Agencies|Swedish Research Council [621-2011-4319]; Swedish Foundation for Strategic Research [ICA10-0002]; Linkoping University; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

    Tilgjengelig fra: 2016-10-26 Laget: 2016-10-21 Sist oppdatert: 2019-01-22
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