| 1. |
- Lum, P Y, et al.
(författare)
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Extracting insights from the shape of complex data using topology
- 2013
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- This paper applies topological methods to study complex high dimensional data sets by extracting shapes (patterns) and obtaining insights about them. Our method combines the best features of existing standard methodologies such as principal component and cluster analyses to provide a geometric representation of complex data sets. Through this hybrid method, we often find subgroups in data sets that traditional methodologies fail to find. Our method also permits the analysis of individual data sets as well as the analysis of relationships between related data sets. We illustrate the use of our method by applying it to three very different kinds of data, namely gene expression from breast tumors, voting data from the United States House of Representatives and player performance data from the NBA, in each case finding stratifications of the data which are more refined than those produced by standard methods.
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| 2. |
- Söderberg, Jeannette A. E., et al.
(författare)
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Insulin-producing cells in the Drosophila brain also express satiety-inducing cholecystokinin-like peptide, drosulfakinin
- 2012
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of meal size and assessing the nutritional value of food are two important aspects of feeding behavior. The mechanisms that regulate these two aspects have not been fully elucidated in Drosophila. Diminished signaling with insulin-like peptides Drosophila insulin-like peptides (DILPs) affects food intake in flies, but it is not clear what signal(s) mediates satiety. Here we investigate the role of DILPs and drosulfakinins (DSKs), cholecystokinin-like peptides, as satiety signals in Drosophila. We show that DSKs and DILPs are co-expressed in insulin-producing cells (IPCs) of the brain. Next we analyzed the effects of diminishing DSKs or DILPs employing the Gal4-UAS system by (1) diminishing DSK-levels without directly affecting DILP levels by targeted Dsk-RNAi, either in all DSK-producing cells (DPCs) or only in the IPCs or (2) expressing a hyperpolarizing potassium channel to inactivate either all the DPCs or only the IPCs, affecting release of both peptides. The transgenic flies were assayed for feeding and food choice, resistance to starvation, and for levels of Dilp and Dsk transcripts in brains of fed and starved animals. Diminishment of DSK in the IPCs alone is sufficient to cause defective regulation of food intake and food choice, indicating that DSK functions as a hormonal satiety signal in Drosophila. Quantification of Dsk and Dilp transcript levels reveals that knockdown of either peptide type affects the transcript levels of the other, suggesting a possible feedback regulation between the two signaling pathways. In summary, DSK and DILPs released from the IPCs regulate feeding, food choice and metabolic homeostasis in Drosophila in a coordinated fashion.
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| 3. |
- Bisch-Knaden, Sonja, et al.
(författare)
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Olfactory coding in five moth species from two families
- 2012
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 215:9, s. 1542-1551
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to determine what impact phylogeny and life history might have on the coding of odours in the brain. Using three species of hawk moths (Sphingidae) and two species of owlet moths (Noctuidae), we visualized neural activity patterns in the antennal lobe, the first olfactory neuropil in insects, evoked by a set of ecologically relevant plant volatiles. Our results suggest that even between the two phylogenetically distant moth families, basic olfactory coding features are similar. But we also found different coding strategies in the moths' antennal lobe; namely, more specific patterns for chemically similar odorants in the two noctuid species than in the three sphingid species tested. This difference demonstrates the impact of the phylogenetic distance between species from different families despite some parallel life history traits found in both families. Furthermore, pronounced differences in larval and adult diet among the sphingids did not translate into differences in the olfactory code; instead, the three species had almost identical coding patterns.
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| 4. |
- Carlsson, Mikael A., et al.
(författare)
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A behavioural operant discrimination model for assessment and pharmacological manipulation of visual function in rats
- 2010
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1321, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- A large number of commercially available drugs are known to cause visual side effects in humans. Therefore, it would be advantageous to screen for alterations in visual function at a pre-clinical stage. Available methods, however, lack control for motivational and motoric side effects. The aim of the present study was therefore to develop a behavioural test to detect and quantify drug-induced visual side effects while simultaneously controlling for other side effects. We here present a novel model based on operant conditioning methodology with a food rewarded two-choice design to assess visual acuity and contrast sensitivity in rats. Rats were trained to discriminate between computer-generated sine-wave gratings and homogenous grey stimuli of equal luminance. They were subsequently tested with novel stimuli differing to training stimuli according to either spatial frequency or contrast. Finally, we tested how visual acuity was affected by oral administration of quinine HCl, a compound known to affect visual function in man. The rats learned to discriminate visual stimuli within 4-5 weeks of twice daily training. A training procedure with moving stimuli achieved faster learning than with static stimuli. The visual detection threshold for discrimination of grating patterns decreased as a function of the contrast level, ranging from a spatial frequency of 0.8 cycles/degree (c/d) at 100% contrast to 0.2 c/d at 12.5%. Administration of quinine HCl was shown to affect the visual acuity threshold in a dose- and time dependent manner. In addition, response rate was affected by quinine administration but temporally isolated from the attenuation of visual acuity demonstrating that this model can separate the visual effects from motoric and motivational side effects.
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| 5. |
- Carlsson, Mikael A., et al.
(författare)
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Distribution of short neuropeptide F and its receptor in neuronal circuits related to feeding in larval Drosophila
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 353:3, s. 511-523
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Tidskriftsartikel (refereegranskat)abstract
- Four forms of short neuropeptide F (sNPF1-4), derived from the gene snpf, have been identified in Drosophila and are known to act on a single G-protein-coupled receptor (sNPFR). Several functions have been suggested for sNPFs in Drosophila, including the regulation of feeding and growth in larvae, the control of insulin signalling and the modulation of neuronal circuits in adult flies. Furthermore, sNPF has been shown to act as a nutritional state-dependent neuromodulator in the olfactory system. The role of sNPF in the larval nervous system is less well known. To analyse sites of action of sNPF in the larva, we mapped the distribution of sNPF- and sNPFR-expressing neurons. In particular, we studied circuits associated with chemosensory inputs and systems involved in the regulation of feeding, including neurosecretory cell systems and the hypocerebral ganglion. We employed a combination of immunocytochemistry and enhancer trap and promoter Gal4 lines to drive green fluorescent protein. We found a good match between the distribution of the receptor and its ligand. However, several differences between the larval and adult systems were observed. Thus, neither sNPF nor its receptor was found in the olfactory (or other sensory) systems in the larva and cells producing insulin-like peptides did not co-express sNPFR, as opposed to results from adults. Moreover, sNPF was expressed in a subpopulation of Hugin cells (second-order gustatory neurons) only in adult flies. We propose that the differences in sNPF signalling between the developmental stages is explained by differences in their feeding behaviour.
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| 6. |
- Carlsson, Mikael A., et al.
(författare)
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Multiple neuropeptides in the Drosophila antennal lobe suggest complex modulatory circuits
- 2010
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 518:16, s. 3359-3380
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Tidskriftsartikel (refereegranskat)abstract
- The fruitfly, Drosophila, is dependent on its olfactory sense in food search and reproduction. Processing of odorant information takes place in the antennal lobes, the primary olfactory center in the insect brain. Besides classical neurotransmitters, earlier studies have indicated the presence of a few neuropeptides in the olfactory system. In the present study we made an extensive analysis of the expression of neuropeptides in the Drosophila antennal lobes by direct profiling using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and immunocytochemistry. Neuropeptides from seven different precursor genes were unambiguously identified and their localization in neurons was subsequently revealed by immunocytochemistry. These were short neuropeptide F, tachykinin related peptide, allatostatin A, myoinhibitory peptide, SIFamide, IPNamide, and myosuppressin. The neuropeptides were expressed in subsets of olfactory sensory cells and different populations of local interneurons and extrinsic (centrifugal) neurons. In some neuron types neuropeptides were colocalized with classical neurotransmitters. Our findings suggest a huge complexity in peptidergic signaling in different circuits of the antennal lobe.
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| 7. |
- Carlsson, Mikael A., et al.
(författare)
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Odour Maps in the Brain of Butterflies with Divergent Host-Plant Preferences
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.
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| 8. |
- Carlsson, Mikael A., et al.
(författare)
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Organization of the olfactory system of Nymphalidae butterflies
- 2013
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 38:4, s. 355-367
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Tidskriftsartikel (refereegranskat)abstract
- Olfaction is in many species the most important sense, essential for food search, mate finding, and predator avoidance. Butterflies have been considered a microsmatic group of insects that mainly rely on vision due to their diurnal lifestyle. However, an emerging number of studies indicate that butterflies indeed use the sense of smell for locating food and oviposition sites. To unravel the neural substrates for olfaction, we performed an anatomical study of 2 related butterfly species that differ in food and host plant preference. We found many of the anatomical structures and pathways, as well as distribution of neuroactive substances, to resemble that of their nocturnal relatives among the Lepidoptera. The 2 species differed in the number of one type of olfactory sensilla, thus indicating a difference in sensitivity to certain compounds. Otherwise no differences could be observed. Our findings suggest that the olfactory system in Lepidoptera is well conserved despite the long evolutionary time since butterflies and moths diverged from a common ancestor.
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| 9. |
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| 10. |
- Kahsai, Lily, et al.
(författare)
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Distribution of metabotropic receptors of serotonin, dopamine, GABA, glutamate, and short neuropeptide F in the central complex of Drosophila
- 2012
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 208, s. 11-26
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Tidskriftsartikel (refereegranskat)abstract
- The central complex is a prominent set of midline neuropils in the insect brain, known to be a higher locomotor control center that integrates visual inputs and modulates motor outputs. It is composed of four major neuropil structures, the ellipsoid body (EB), fan-shaped body (FB), noduli (NO), and protocerebral bridge (PB). In Drosophila different types of central complex neurons have been shown to express multiple neuropeptides and neurotransmitters; however, the distribution of corresponding receptors is not known. Here, we have mapped metabotropic, G-protein–coupled receptors (GPCRs) of several neurotransmitters to neurons of the central complex. By combining immunocytochemistry with GAL4 driven green fluorescent protein, we examined the distribution patterns of six different GPCRs: two serotonin receptor subtypes (5-HT1B and 5-HT7), a dopamine receptor (DopR), the metabotropic GABAB receptor (GABABR), the metabotropic glutamate receptor (DmGluRA) and a short neuropeptide F receptor (sNPFR1). Five of the six GPCRs were mapped to different neurons in the EB (sNPFR1 was not seen). Different layers of the FB express DopR, GABABR, DmGluRA, and sNPFR1, whereas only GABABR and DmGluRA were localized to the PB. Finally, strong expression of DopR and DmGluRA was detected in the NO. In most cases the distribution patterns of the GPCRs matched the expression of markers for their respective ligands. In some nonmatching regions it is likely that other types of dopamine and serotonin receptors or ionotropic GABA and glutamate receptors are expressed. Our data suggest that chemical signaling and signal modulation are diverse and highly complex in the different compartments and circuits of the Drosophila central complex. The information provided here, on receptor distribution, will be very useful for future analysis of functional circuits in the central complex, based on targeted interference with receptor expression.
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