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- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 2. |
- Asker, Mohammed, et al.
(författare)
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Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects
- 2023
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:3, s. 856-877
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesOxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure.Methods and ResultsWe first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IP-injected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B-12 (fCy5-OT-B-12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBB-impermeable OT (OT-B-12), with equipotent binding at OT-R in vitro. In vivo, IP-injected OT and OT-B-12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B-12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B-12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression.ConclusionsTogether our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT-R may be a viable strategy to achieve appetite suppression with better patient outcomes.
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| 3. |
- Pecunia, Vincenzo, et al.
(författare)
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Roadmap on energy harvesting materials
- 2023
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Ingår i: Journal of Physics. - : IOP Publishing. - 2515-7639. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
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| 10. |
- Asker, C, et al.
(författare)
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Use of antiemetic drugs during pregnancy in Sweden
- 2005
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 61:12, s. 899-906
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than one-half of all pregnant women suffer from nausea and vomiting during pregnancy (NVP), primarily during the first trimester. Methods: Prospectively ascertained information on drug use during pregnancy was obtained from the Swedish Medical Birth Register during the period July 1, 1995 to 2002. Antiemetics (antiemetic antihistamines, dopamine modulators, and ondansetron) primarily used for NVP were studied, and women reporting the use of these drugs were compared with all women who gave birth during the study period. Results: Use of these antiemetics was reported in 4.5% of the pregnant women - 86% of whom reported their use before the first antenatal visit (usually weeks 10-12). Meclozine, followed by other antihistamines, accounted for 68% of the drugs reported. Young maternal age, multiparity, non-smoking, and a period of unwanted childlessness increased the probability of using any of the antiemetics during pregnancy. Women with a low education used these drugs more often than women with a relatively higher education. Neonates born to women who used any of the antiemetics had a reduced risk for low birthweight, prematurity, being small-for-gestational age, and having a malformation. No specific differences were observed with respect to the outcome following a comparison of different antiemetic drugs. Conclusions: Women using antiemetics as a rule have a better delivery outcome than other women, probably due to an effect of a well-functioning placenta, which is associated with NVP. There were no signs of any significant teratogenicity of the drugs studied, but for some drugs the number of exposures was low.
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