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Sökning: WFRF:(Pfaff Michael)

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1.
  • Zhukova, Nataliya, et al. (författare)
  • WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
  • 2014
  • Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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2.
  • Abb, Marcel J.S., et al. (författare)
  • Thermal Stability of Single-Crystalline IrO2(110) Layers : Spectroscopic and Adsorption Studies
  • 2020
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 124:28, s. 15324-15336
  • Tidskriftsartikel (refereegranskat)abstract
    • The interaction of ultrathin single-crystalline IrO2(110) films with the gas phase proceeds via the coordinatively unsaturated sites (cus), in particular Ircus, the undercoordinated oxygen species on-top O (Oot) that are coordinated to Ircus, and bridging O (Obr). With the combination of different experimental techniques, such as thermal desorption spectroscopy, scanning tunneling microscopy (STM), high-resolution core-level spectroscopy (HRCLS), infrared spectroscopy, and first-principles studies employing density functional theory calculations, we are able to elucidate surface properties of single-crystalline IrO2(110). We provide spectroscopic fingerprints of the active surface sites of IrO2(110). The freshly prepared IrO2(110) surface is virtually inactive toward gas-phase molecules. The IrO2(110) surface needs to be activated by annealing to 500-600 K under ultrahigh vacuum (UHV) conditions. In the activation step, Ircus sites are liberated from on-top oxygen (Oot) and monoatomic Ir metal islands are formed on the surface, leading to the formation of a bifunctional model catalyst. Vacant Ircus sites of IrO2(110) allow for strong interaction and accommodation of molecules from the gas phase. For instance, CO can adsorb atop on Ircus and water forms a strongly bound water layer on the activated IrO2(110) surface. Single-crystalline IrO2(110) is thermally not very stable although chemically stable. Chemical reduction of IrO2(110) by extensive CO exposure at 473 K is not observed, which is in contrast to the prototypical RuO2(110) system.
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3.
  • Goyret, Joaquin, et al. (författare)
  • Flexible responses to visual and olfactory stimuli by foraging Manduca sexta: larval nutrition affects adult behaviour
  • 2009
  • Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 276:1668, s. 2739-2745
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we show that the consequences of deficient micronutrient (beta-carotene) intake during larval stages of Manduca sexta are carried across metamorphosis, affecting adult behaviour. Our manipulation of larval diet allowed us to examine how developmental plasticity impacts the interplay between visual and olfactory inputs on adult foraging behaviour. Larvae of M. sexta were reared on natural (Nicotiana tabacum) and artificial laboratory diets containing different concentrations of beta-carotene (standard diet, low beta-carotene, high beta-carotene and cornmeal). This vitamin-A precursor has been shown to be crucial for photoreception sensitivity in the retina of M. sexta. After completing development, post-metamorphosis, starved adults were presented with artificial feeders that could be either scented or unscented. Regardless of their larval diet, adult moths fed with relatively high probabilities on scented feeders. When feeders were unscented, moths reared on tobacco were more responsive than moths reared on beta-carotene-deficient artificial diets. Strikingly, moths reared on artificial diets supplemented with increasing amounts of beta-carotene (low beta and high beta) showed increasing probabilities of response to scentless feeders. We discuss these results in relationship to the use of complex, multi-modal sensory information by foraging animals.
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4.
  • Goyret, Joaquin, et al. (författare)
  • Why do Manduca sexta feed from white flowers? Innate and learnt colour preferences in a hawkmoth
  • 2008
  • Ingår i: Naturwissenschaften. - : Springer Science and Business Media LLC. - 1432-1904 .- 0028-1042. ; 95:6, s. 569-576
  • Tidskriftsartikel (refereegranskat)abstract
    • Flower colour is an important signal used by flowering plants to attract pollinators. Many anthophilous insects have an innate colour preference that is displayed during their first foraging bouts and which could help them locate their first nectar reward. Nevertheless, learning capabilities allow insects to switch their colour preferences with experience and thus, to track variation in floral nectar availability. Manduca sexta, a crepuscular hawkmoth widely studied as a model system for sensory physiology and behaviour, visits mostly white, night-blooming flowers lacking UV reflectance throughout its range in the Americas. Nevertheless, the spectral sensitivity of the feeding behaviour of naive moths shows a narrow peak around 450 nm wavelengths, suggesting an innate preference for the colour blue. Under more natural conditions (i.e. broader wavelength reflectance) than in previous studies, we used dual choice experiments with blue- and white-coloured feeders to investigate the innate preference of naive moths and trained different groups to each colour to evaluate their learning capabilities. We confirmed the innate preference of M. sexta for blue and found that these moths were able to switch colour preferences after training experience. These results unequivocally demonstrate that M. sexta moths innately prefer blue when presented against white flower models and offer novel experimental evidence supporting the hypothesis that learning capabilities could be involved in their foraging preferences, including their widely observed attraction to white flowers in nature.
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5.
  • Hoffman, Lindsey M., et al. (författare)
  • Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG) : A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries
  • 2018
  • Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:19, s. 1963-1972
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeDiffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs).Materials and MethodsData abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.ResultsAmong 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration (P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002).ConclusionWe report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.
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9.
  • Potier, Simon, et al. (författare)
  • How fast can raptors see?
  • 2020
  • Ingår i: The Journal of experimental biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 223
  • Tidskriftsartikel (refereegranskat)abstract
    • Birds, and especially raptors, are highly visual animals. Some of them have the highest spatial resolving power known in the animal kingdom, allowing prey detection at distance. While many raptors visually track fast-moving and manoeuvrable prey, requiring high temporal resolution, this aspect of their visual system has never been studied before. In this study, we estimated how fast raptors can see, by measuring the flicker fusion frequency of three species with different lifestyles. We found that flicker fusion frequency differed among species, being at least 129 Hz in the peregrine falcon, Falco peregrinus, 102 Hz in the saker falcon, Falco cherrug, and 81 Hz in the Harris's hawk, Parabuteo unicinctus We suggest a potential link between fast vision and hunting strategy, with high temporal resolution in the fast-flying falcons that chase fast-moving, manoeuvrable prey and a lower resolution in the Harris's hawk, which flies more slowly and targets slower prey.
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10.
  • Raguso, Robert A., et al. (författare)
  • Floral biology of North American Oenothera sect. Lavauxia (Onagraceae): Advertisements, rewards, and extreme variation in floral depth
  • 2007
  • Ingår i: Annals of the Missouri Botanical Garden. - 0026-6493. ; 94:1, s. 236-257
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the floral biology of five North American members of Oenothera L. sect. Lavauxia (Spach) Endl. (Onagraceae L.) in field and common greenhouse settings. Oenothera sect. Lavauxia floral morphology ranges from small, cleistogamous flowers (O. flava subsp. flava (A. Nels.) Garrett in Garrett) to sonic of the longest-tubed flowers in North America (O. flava subsp. taraxacoides (Wooton & Standl.) W. L. Wagner). Our goal was to compare qualitative and quantitative aspects of floral advertisement and reward among taxa in section Lavauxia. All taxa are night-blooming and self-compatible, have yellow petals with ultraviolet reflectance, and produce floral scents dominated by nitrogenous compounds and monoterpenes. Methyl nicotinate is present in the fragrances of all taxa of section Lavauxia regardless of flower size or putative mating system. Because this floral volatile is largely absent from other Oenothera species, we hypothesize that it is a synapomorphy for section Lavauxia. The rare O. acutissima W. L. Wagner, which is endemic to the Uintah Mountains, is polymorphic for odors dominated by linalool- or ocimene-derived compounds). Field observations in its type locality in northeastern Utah, U.S.A., revealed frequent floral visitation by crepuscular hawkmoths during the first 1.5 hours after anthesis, a pattern common to O. flava subsp. taraxacoides and other large-flowered Oenothera throughout western North America. Quantitative aspects of floral advertisement (flower size, scent emission) and reward (nectar volume) are dramatically reduced in putatively autogamous taxa (O. flava subsp. flava, O. triloba Nutt.). whereas qualitative aspects (flower color, scent, and nectar chemistry) remain comparable. All taxa could be distinguished through ordination of characters related to flower size, herkogamy. and scent chemistry. Extreme nectar tube length variation across the range of O. flava renders this an excellent model system for measuring the costs and mechanisms of shifts between outcrossing and autogamy.
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