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- Vicente Carrillo, Alejandro, 1989-
(författare)
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Sperm Membrane Channels, Receptors and Kinematics : Using boar spermatozoa for drug toxicity screening
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Internal fertilization usually implies that a spermatozoon, with intact attributes for zygote formation, passes all hurdles during its transport through the female genitalia and reaches the oocyte. During this journey, millions to billions of other spermatozoa perish. Spermatozoa are highly differentiated motile cells without synthetic capabilities. They generate energy via glycolysis and oxidative phosphorylation to sustain motility and to maintain the stability and functionality of their plasma membrane. In vivo, they spend their short lifespan bathing in female genital tract fluids of different origins, or are in vitro exposed to defined media during diverse sperm handling i.e. extension, cryopreservation, in vitro fertilization, etc. Being excitable cells, spermatozoa respond in vivo to various stimuli during pre-fertilization (capacitation, hyperactivation, oocyte location) and fertilization (acrosome reaction, interaction with the oocyte) events, mediated via diverse membrane ion-conducting channels and ligand-gated receptors. The present Thesis has mapped the presence and reactivity (sperm intactness and kinematics) of selected receptors, water and ion channels in ejaculated boar spermatozoa. The final aim was to find a relevant alternative cell type for in vitro bioassays that could ease the early scrutiny of candidate drugs as well as decreasing our needs for experimental animals according to the 3R principles. Spermatozoa are often extended, cooled and thawed to warrant their availability as fertile gametes for breeding or in vitro testing. Such manipulations stress the cells via osmotic variations and hence spermatozoa need to maintain membrane intactness by controlling the exchange of water and the common cryoprotectant glycerol, via aquaporins (AQPs). Both AQPs-7 and -9 were studied for membrane domain changes in cauda- and ejaculated spermatozoa (un-processed, extended, chilled or frozen-thawed). While AQP-9 maintained location through source and handling, thawing of ejaculated spermatozoa clearly relocated the labelling of AQP-7, thus appearing as a relevant marker for non-empirical studies of sperm cryopreservation. Alongside water, spermatozoa interact with calcium (Ca2+) via the main Ca2+ sperm channel CatSper. Increments in intracellular Ca2+ initiate motility hyperactivation and the acrosome reaction. The four subunits of the CatSper channel were present in boar spermatozoa, mediating changes in sperm motility under in vitro capacitation-inducing conditions (increased extracellular Ca2+ availability and bicarbonate) or challenge by the CatSper antagonists mibefradil and NNC 55-0396. Uterine and oviduct fluids are richest in endogenous opioids as β-endorphins during mating and ovulation. Both μ- and δ- opioid receptors were present in boar spermatozoa modulating sperm motility, as in vitro challenge with known agonists (μ: morphine; δ: DPDPE and κ: U 50488) and antagonists (μ: naloxone; δ: naltrindole and κ: nor-binaltrorphimine) showed that the μ-opioid receptor maintained or increased motility while the δ-opioid receptor mediated decreased motility over time. Finally, boar spermatozoa depicted dose-response effects on sperm kinematics and mitochondrial potential following in vitro challenge with 130 pharmacological drugs and toxic compounds as well as with eight known mito-toxic compounds. In conclusion, boar spermatozoa expressing functional water (AQPs-7 and -9) and ion (CatSper 1-4) channels as well as μ- and δ-opioid receptors are able to adapt to stressful environmental variations, capacitation and pharmacological compounds and drug components. Ejaculated sperm suspensions are easily and painlessly obtained from breeding boars, and are suitable biosensors for in vitro drug-induced testing, complying with the 3R principles of reduction and replacement of experimental animals, during early toxicology screening.
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| 2. |
- Landberg, Rikard, 1981, et al.
(författare)
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Avenanthramides as lipoxygenase inhibitors
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Avenanthramides (AVAs) present in oats are amides of anthranilic and cinnamic acids. AVAs are potent antioxidants and have anti-inflammatory properties. There are various potential mechanisms for their anti-inflammatory effects, including inhibition of lipoxygenases (LOX), which catalyse oxygenation of polyunsaturated fatty acids into potent signal molecules involved in inflammatory processes. In this study, AVAs were screened for LOX inhibition in vitro and structure-activity relationships were examined. Twelve different AVAs at 0.6 mM were tested as LOX inhibitors. The corresponding free cinnamic acids, the AVA analogue Tranilast® and the known LOX inhibitor trans-resveratrol were included for comparison. It was found that AVAs comprising caffeic or sinapic acid exhibited significant lipoxygenase inhibition (60–90%) (P < 0.05), whereas low or no inhibition was observed with AVAs containing p-coumaric or ferulic acid. No difference in inhibition was seen on comparing AVAs with their free corresponding cinnamic acids, which implies that the anthranilic acid part of the avenanthramide molecule does not affect inhibition. Trans-resveratrol showed inhibition, whereas no inhibition was seen for Tranilast® at the concentrations used in this study. This study suggests that aventahtramides comprising caffeic acid or sinapic acid partly exert their antioxidant and anti-inflammatory effects via lipoxygenase inhibition.
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| 3. |
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| 4. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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| 5. |
- Zubair, Muhammad, et al.
(författare)
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Effects of Plantago major L. leaf extracts on oral epithelial cells in a scratch assay
- 2012
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Ingår i: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 141:3, s. 825-830
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Tidskriftsartikel (refereegranskat)abstract
- Aim of study The present study was undertaken to evaluate the effects from different leaf extracts of the traditional medicinal herb Plantago major L. (plantain) on cell proliferation and migration in vitro, as a test for potential wound healing properties. Materials and methods Water and ethanol-based extracts were prepared from Plantago major fresh and dried leaves, and tested in vitro in a scratch assay with oral epithelial cells. Results The scratch assay produced reliable results after 18 h. Most of the tested extracts increased the proliferation/migration of the oral epithelial cells compared to the negative control. A concentration of 1.0 mg/mL (on dry weight basis) appears to be optimal regardless of type of extract, and among the alternatives, 0.1 mg/mL was always better than 10 mg/mL. Ethanol-based extracts with a concentration of 10 mg/mL had very detrimental effects on cell proliferation/migration. At the other two concentrations, ethanol-based extracts had the most beneficial effect, followed by water extracts of fresh leaves, ethanol plus water extracts of dried leaves and, finally, water extracts of dried leaves. This study suggests that both the water extracts and the more polyphenol-rich ethanol-based extracts of Plantago major leaves have medicinal properties. Further research is, however, needed to determine what compounds are responsible for the wound healing effects.
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| 6. |
- Esmaily, Mohsen, 1987, et al.
(författare)
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Oxidation and electrical properties of chromium–iron alloys in a corrosive molten electrolyte environment
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Chromium–iron (CrFe) binary alloys have recently been proposed to serve as the “inert” anode for molten oxide electrolysis (MOE). Herein, the effects of anodic polarization on physical and functional properties of CrFe anodes in the corrosive environment of MOE are studied via empirical observations and theoretical calculations. The findings indicate that the alloys form an inner chromia–alumina solid-solution covered by an MgCr2O4 spinel layer. A survey into the electrical properties of the detected oxides suggests that the layered oxide scale function as an efficient conductor of electricity at elevated temperature. The formation mechanism of the oxides is also investigated.
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| 7. |
- Gupta, Swarnim, 1984, et al.
(författare)
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The development of a novel ferric phytate compound for iron fortification of bouillons (part I)
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In a series of two studies, we report the development (this study) and evaluation (part II) of a novel ferric phytate compound designed as a condiment iron fortificant. Condiments are used as iron fortification vehicles to reduce the prevalence of iron deficiency. The challenge for iron fortificants in e.g. a bouillon matrix is to avoid undesired sensory effects and to ensure a reasonable cost. We added phytic acid to chelate iron, and hydrolysed protein to counteract the inhibiting effect of phytic acid on iron bioaccessibility. We characterised four novel ferric phytate compounds, destabilised by hydrolysed plant protein or amino acids. Colour stability of fortified bouillons with ferric phytate compounds was superior to bouillons fortified with ferrous sulfate. The iron-phytate-hydrolysed corn protein compound (Fe-PAHCP) resulted in highest cellular ferritin induction in Caco-2 cells, in both vegetable (36.1 ± 13.40 ng/mg protein) and chicken (73.9 ± 19.93 ng/mg protein) bouillon matrices as observed in the human Caco-2/ HepG2 cell model. Iron uptake (as estimated by ferritin production) from the Fe-PA-HCP compound was about 55% (chicken bouillon) and 66% (vegetable bouillon) of the iron uptake from ferrous sulfate. Based on this study, the Fe-PA-HCP compound was chosen for further evaluation (part II).
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| 8. |
- Steer, Philippe, et al.
(författare)
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Earthquake statistics changed by typhoon-driven erosion
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Tectonics and climate-driven surface processes govern the evolution of Earth’s surface topography. Topographic change in turn influences lithospheric deformation, but the elementary scale at which this feedback can be effective is unclear. Here we show that it operates in a single weather-driven erosion event. In 2009, typhoon Morakot delivered ~ 3 m of precipitation in southern Taiwan, causing exceptional landsliding and erosion. This event was followed by a step increase in the shallow (< 15 km depth) earthquake frequency lasting at least 2.5 years. Also, the scaling of earthquake magnitude and frequency underwent a sudden increase in the area where mass wasting was most intense. These observations suggest that the progressive removal of landslide debris by rivers from southern Taiwan has acted to increase the crustal stress rate to the extent that earthquake activity was demonstrably affected. Our study offers the first evidence of the impact of a single weather-driven erosion event on tectonics.
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| 9. |
- Vieira, Taian Martins, et al.
(författare)
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Specificity of surface EMG recordings for gastrocnemius during upright standing
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- The relatively large pick-up volume of surface electrodes has for long motivated the concern that muscles other than that of interest may contribute to surface electromyograms (EMGs). Recent findings suggest however the pick-up volume of surface electrodes may be smaller than previously appreciated, possibly leading to the detection of surface EMGs insensitive to muscle activity. Here we combined surface and intramuscular recordings to investigate how comparably action potentials from gastrocnemius and soleus are represented in surface EMGs detected with different inter-electrode distances. We computed the firing instants of motor units identified from intramuscular EMGs detected from gastrocnemius and soleus while five participants stood upright. We used these instants to trigger and average surface EMGs detected from multiple skin regions along gastrocnemius. Results from 66 motor units (whereof 31 from gastrocnemius) revealed the surface-recorded amplitude of soleus action potentials was 6% of that of gastrocnemius and did not decrease for inter-electrode distances smaller than 4 cm. Gastrocnemius action potentials were more likely detected for greater inter-electrode distances and their amplitude increased steeply up to 5 cm inter-electrode distance. These results suggest that reducing inter-electrode distance excessively may result in the detection of surface EMGs insensitive to gastrocnemius activity without substantial attenuation of soleus crosstalk.
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| 10. |
- Visser, Dennis, et al.
(författare)
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Embossed Mie resonator arrays composed of compacted TiO2 nanoparticles for broadband anti-reflection in solar cells
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Mie resonator arrays formed by embossing titanium dioxide (TiO2) nanoparticles (NPs) from solution are investigated as optical coatings for anti-reflection applications. Compacted nanoparticle assemblies offer unique possibilities to tailor the effective refractive index (RI). Here, we demonstrate a simple table-top, low pressure, and low temperature method to fabricate structured optical coatings. TiO2 nanostructures in the form of nanodisks support Mie resonances in the visible wavelength spectrum and exhibit strong forward scattering into the high index substrates, making them suitable as broadband anti-reflection coatings for solar cells. TiO2 NP-based nanodisk arrays are designed, fabricated, and characterized regarding their anti-reflection properties on Si, GaAs, and InP substrates and solar cells. Detailed finite-difference time-domain simulations are performed to optimize the TiO2 NP-based Mie resonator arrays for the broadband anti-reflection as well as to explain the measured reflectance spectra. The solar-weighted reflectance is used as a figure of merit (FoM). TiO2 nanodisk arrays on Si show a FoM of ~ 7% in the 400–1,100 nm wavelength spectrum; similar values are obtained for GaAs and InP substrates. TiO2 nanodisk arrays embossed directly on prefabricated planar single-junction Si, GaAs, and InP solar cells result in an appreciable increase (~ 1.3 times) in the short-circuit current densities.
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