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- Niemelä, E., et al.
(författare)
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Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : ELSEVIER. - 0939-6411 .- 1873-3441. ; 148, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors.
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- Moores, John E., et al.
(författare)
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Atmospheric movies acquired at the Mars Science Laboratory landing site : Cloud Morphology, Frequency and Significance to the Gale Crater Water Cycle and Phoenix Mission Results
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 55:9, s. 2217-2238
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first 360 sols (LS 150° to 5°), representing just over half a Martian year, of atmospheric monitoring movies acquired using the NavCam imager from the Mars Science Laboratory (MSL) Rover Curiosity. Such movies reveal faint clouds that are difficult to discern in single images. The data set acquired was divided into two different classifications depending upon the orientation and intent of the observation. Up to sol 360, 73 Zenith Movies and 79 Supra-Horizon Movies have been acquired and time-variable features could be discerned in 25 of each. The data set from MSL is compared to similar observations made by the Surface Stereo Imager (SSI) onboard the Phoenix Lander and suggests a much drier environment at Gale Crater (4.6°S) during this season than was observed in Green Valley (68.2°N) as would be expected based on latitude and the global water cycle. The optical depth of the variable component of clouds seen in images with features are up to 0.047 ± 0.009 with a granularity to the features observed which averages 3.8 degrees. MCS also observes clouds during the same period of comparable optical depth at 30 and 50 km that would suggest a cloud spacing of 2.0 to 3.3 km. Multiple motions visible in atmospheric movies support the presence of two distinct layers of clouds. At Gale Crater, these clouds are likely caused by atmospheric waves given the regular spacing of features observed in many Zenith movies and decreased spacing towards the horizon in sunset movies consistent with clouds forming at a constant elevation. Reanalysis of Phoenix data in the light of the NavCam equatorial dataset suggests that clouds may have been more frequent in the earlier portion of the Phoenix mission than was previously thought.
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- Butlin, Roger, 1955, et al.
(författare)
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PARALLEL EVOLUTION OF LOCAL ADAPTATION AND REPRODUCTIVE ISOLATION IN THE FACE OF GENE FLOW
- 2014
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Ingår i: Evolution. - : Wiley. - 0014-3820. ; 68:4, s. 935-949
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Tidskriftsartikel (refereegranskat)abstract
- Parallel evolution of similar phenotypes provides strong evidence for the operation of natural selection. Where these phenotypes contribute to reproductive isolation, they further support a role for divergent, habitat-associated selection in speciation. However, the observation of pairs of divergent ecotypes currently occupying contrasting habitats in distinct geographical regions is not sufficient to infer parallel origins. Here we show striking parallel phenotypic divergence between populations of the rocky-shore gastropod, Littorina saxatilis, occupying contrasting habitats exposed to either wave action or crab predation. This divergence is associated with barriers to gene exchange but, nevertheless, genetic variation is more strongly structured by geography than by ecotype. Using approximate Bayesian analysis of sequence data and amplified fragment length polymorphism markers, we show that the ecotypes are likely to have arisen in the face of continuous gene flow and that the demographic separation of ecotypes has occurred in parallel at both regional and local scales. Parameter estimates suggest a long delay between colonization of a locality and ecotype formation, perhaps because the postglacial spread of crab populations was slower than the spread of snails. Adaptive differentiation may not be fully genetically independent despite being demographically parallel. These results provide new insight into a major model of ecologically driven speciation.
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