| 1. |
- Maier, Hannes, et al.
(författare)
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Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
- 2022
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Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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| 2. |
- Soliveres, Santiago, et al.
(författare)
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Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
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Tidskriftsartikel (refereegranskat)abstract
- Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
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| 3. |
- Soliveres, Santiago, et al.
(författare)
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Locally rare species influence grassland ecosystem multifunctionality
- 2016
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Tidskriftsartikel (refereegranskat)abstract
- Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
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| 4. |
- Adams, JC, et al.
(författare)
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Characterisation of Drosophila thrombospondin defines an early origin of pentameric thrombospondins
- 2003
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Ingår i: Journal of Molecular Biology. - 1089-8638. ; 328:2, s. 479-494
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Tidskriftsartikel (refereegranskat)abstract
- Thrombospondins (TSPs) are multidomain oligomers that have complex roles in cell interactions and tissue organisation. The five vertebrate TSPs comprise two subgroups, A and B, that are assembled as trimers or pentamers, respectively. An invertebrate TSP was recently discovered in Drosophila melanogaster, but there is no knowledge of the oligomerisation status or properties of this molecule. We developed by bioinformatics a new dataset containing the single TSP of Drosophila melanogaster and four other newly identified invertebrate TSPs to examine the phylogenetic relationships of TSPs. These analyses clearly indicate pentamerisation as an early attribute of TSPs. We demonstrate experimentally that D. melanogaster TSP is assembled as a pentamer, has heparin-binding activity and is a component of extracellular matrix (ECM). During embryogenesis, the TSP transcript is concentrated at muscle attachment sites and is expressed by a subset of myoblasts and in imaginal discs. These novel results establish TSPs as highly conserved ECM components in both invertebrates and vertebrates and open fresh perspectives on the conservation of structure and biological function within this family
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| 5. |
- Ali, Reda, et al.
(författare)
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Structural conservation of the salivary gland-specific slalom gene in the blowfly Lucilia sericata
- 2005
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Ingår i: Development, Genes and Evolution. - : Springer Science and Business Media LLC. - 0949-944X .- 1432-041X. ; 215:10, s. 537-543
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Tidskriftsartikel (refereegranskat)abstract
- Glycosylation and sulfation are two of the essential post-translational modifications of proteins. The slalom gene encodes a 3'-phosphoadenosine 5'-phosphosulfate transporter, a conserved protein found in organisms as diverse as plants and humans and required for sulfation of proteins. In Drosophila, slalom is exclusively expressed in salivary glands, which is unexpected, taken into account the general function for sulfation of proteins. In this paper, we present a detailed description of the slalom gene in a large insect, the blowfly Lucilia sericata. Our data demonstrate that the slalom gene structure, the protein and the expression pattern are highly conserved between Lucilia and Drosophila. Lucilia slalom promoter analysis, using transgenic Drosophila, demonstrates that the Lucilia slalom promoter can faithfully mimic the expression pattern of both Lucilia and Drosophila slalom in salivary glands. Taken together, these data show the structure and the transcriptional cis-regulatory elements of the slalom gene to be unchanged during evolution, despite the 100 million years of divergence between the two insects. Moreover, it suggests that the salivary gland-specific expression of slalom bears an important and conserved function for sulfation of specific macromolecules.
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| 6. |
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| 7. |
- Baeg, Gyeong-Hun, et al.
(författare)
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Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless
- 2001
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Ingår i: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 128:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies in Drosophila have shown that heparan sulfate proteoglycans (HSPGs) are required for Wingless (Wg/Wnt) signaling. In addition, genetic and phenotypic analyses have implicated the glypican gene daily in this process. Here, we report the identification of another Drosophila glypican gene, daily-like (dly) and show that it is also involved in Wg signaling. Inhibition of dly gene activity implicates a function for DLY in Wg reception and we show that overexpression of DLY leads to an accumulation of extracellular Wg. We propose that DLY plays; a role in the extracellular distribution of Wg. Consistent with this model, a dramatic decrease of extracellular Wg was detected in clones of cells that are deficient in proper glycosaminoglycan biosynthesis. We conclude that HSPGs play an important role in organizing the extracellular distribution of Wg.
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| 8. |
- Baumgartner, Ruth, et al.
(författare)
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Impact of post-hepatectomy liver failure on morbidity and short- and long-term survival after major hepatectomy
- 2022
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Post-hepatectomy liver failure (PHLF) is one of the most serious postoperative complications after hepatectomy. The aim of this study was to assess the impact of the International Study Group of Liver Surgery (ISGLS) definition of PHLF on morbidity and short- and long-term survival after major hepatectomy. Methods This was a retrospective review of all patients who underwent major hepatectomy (three or more liver segments) for various liver tumours between 2010 and 2018 at two Swedish tertiary centres for hepatopancreatobiliary surgery. Descriptive statistics, regression models, and survival analyses were used. Results A total of 799 patients underwent major hepatectomy, of which 218 patients (27 per cent) developed ISGLS-defined PHLF, including 115 patients (14 per cent) with ISGLS grade A, 76 patients (10 per cent) with grade B, and 27 patients (3 per cent) with grade C. The presence of cirrhosis, perihilar cholangiocarcinoma, and gallbladder cancer, right-sided hemihepatectomy and trisectionectomy all significantly increased the risk of clinically relevant PHLF (grades B and C). Clinically relevant PHLF increased the risk of 90-day mortality and was associated with impaired long-term survival. ISGLS grade A had more major postoperative complications compared with no PHLF but failed to be an independent predictor of both 90-day mortality and long-term survival. The impact of PHLF grade B/C on long-term survival was no longer present in patients surviving the first 90 days after surgery. Conclusions The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival; however, even ISGLS grade A had clinical implications. The aim was to assess the ISGLS criteria for post-hepatectomy liver failure (PHLF) in a cohort of patients with major hepatectomy. The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival.
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| 9. |
- Baumgartner, Stefan, et al.
(författare)
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Discovery of Teneurins
- 2019
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 13, s. 1-9
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Forskningsöversikt (refereegranskat)abstract
- Teneurins were first discovered and published in 1993 and 1994, in Drosophila melanogaster as Ten-a and Ten-m. They were initially described as cell surface proteins, and as pair-rule genes. Later, they proved to be type II transmembrane proteins, and not to be pair-rule genes. Ten-m might nonetheless have had an ancestral function in clock-based segmentation as a Ten-m oscillator. The turn of the millennium saw a watershed of vertebrate Teneurin discovery, which was soon complemented by Teneurin protein annotations from whole genome sequence publications. Teneurins encode proteins with essentially invariant domain order and size. The first years of Teneurin studies in many experimental systems led to key insights, and a unified picture, of Teneurin proteins.
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| 10. |
- Baumgartner, Stefan
(författare)
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Editorial note to the last issue of Hereditas.
- 2015
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223 .- 0018-0661. ; 151:6, s. 109-109
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 12. |
- Baumgartner, Stefan
(författare)
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Revisiting bicoid function : complete inactivation reveals an additional fundamental role in Drosophila egg geometry specification
- 2024
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Ingår i: Hereditas. - 0018-0661. ; 161:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The bicoid (bcd) gene in Drosophila has served as a paradigm for a morphogen in textbooks for decades. Discovered in 1986 as a mutation affecting anterior development in the embryo, its expression pattern as a protein gradient later confirmed the prediction from transplantation experiments. These experiments suggested that the protein fulfills the criteria of a true morphogen, with the existence of a homeodomain crucial for activation of genes along the anterior-posterior axis, based on the concentration of the morphogen. The bcd gene undergoes alternative splicing, resulting in, among other isoforms, a small and often neglected isoform with low abundance, which lacks the homeodomain, termed small bicoid (smbcd). Most importantly, all known classical strong bcd alleles used in the past to determine bcd function apparently do not affect the function of this isoform. Results: To overcome the uncertainty regarding which isoform regulates what, I removed the bcd locus entirely using CRISPR technology. bcdCRISPR eggs exhibited a short and round appearance. The phenotype could be ascribed to smbcd because all bcd alleles affecting the function of the major transcript, termed large bicoid (lgbcd) showed normally sized eggs. Several patterning genes for the embryo showed expression in the oocyte, and their expression patterns were altered in bcdCRISPR oocytes. In bcdCRISPR embryos, all downstream segmentation genes showed altered expression patterns, consistent with the expression patterns in “classical” alleles; however, due to the altered egg geometry resulting in fewer blastoderm nuclei, additional constraints came into play, further affecting their expression patterns. Conclusions: This study unveils a novel and fundamental role of bcd in shaping the egg’s geometry. This discovery demands a comprehensive revision of our understanding of this important patterning gene and prompts a reevaluation of past experiments conducted under the assumption that bcd mutants were bcdnull-mutants.
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| 13. |
- Baumgartner, Stefan
(författare)
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Seeing is believing : the Bicoid protein reveals its path
- 2018
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- In this commentary, I will review the latest findings on the Bicoid (Bcd) morphogen in Drosophila, a paradigm for gradient formation taught to biology students for more than two decades. "Seeing is believing" also summarizes the erroneous steps that were needed to elucidate the mechanisms of gradient formation and the path of movement of Bcd. Initially proclaimed as a dogma in 1988 and later incorporated into the SDD model where the broad diffusion of Bcd throughout the embryo was the predominant step leading to gradient formation, the SDD model was irrefutable for more than two decades until first doubts were raised in 2007 regarding the diffusion properties of Bcd associated with the SDD model. This led to re-thinking of the issue and the definition of a new model, termed the ARTS model which could explain most of the physical constraints that were inherently associated with the SDD model. In the ARTS model, gradient formation is mediated by the mRNA which is redistributed along cortical microtubules to form a mRNA gradient which is translated to form the protein gradient. Contrary to the SDD model, there is no Bcd diffusion from the tip. The ARTS model is also compatible with the observed cortical movement of Bcd. I will critically compare the SDD and the ARTS models as well as other models, analyze the major differences, and highlight the path where Bcd is localized during early nuclear cycles.
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| 14. |
- Baumgartner, Stefan, et al.
(författare)
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The discoidin domain family revisited : new members from prokaryotes and a homology-based fold prediction
- 1998
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 7:7, s. 31-1626
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Tidskriftsartikel (refereegranskat)abstract
- Members of the discoidin (DS) domain family, which includes the C1 and C2 repeats of blood coagulation factors V and VIII, occur in a great variety of eukaryotic proteins, most of which have been implicated in cell-adhesion or developmental processes. So far, no three-dimensional structure of a known example of this extracellular module has been determined, limiting the usefulness of identifying a new sequence as member of this family. Here, we present results of a recent search of the protein sequence database for new DS domains using generalized profiles, a sensitive multiple alignment-based search technique. Several previously unrecognized DS domains could be identified by this method, including the first examples from prokaryotic species. More importantly, we present statistical, structural, and functional evidence that the D1 domain of galactose oxidase whose three-dimensional structure has been determined at 1.7 A resolution, is a distant member of this family. Taken together, these findings significantly expand the concept of the DS domain, by extending its taxonomic range and by implying a fold prediction for all its members. The proposed alignment with the galactose oxidase sequence makes it possible to construct homology-based three-dimensional models for the most interesting examples, as illustrated by an accompanying paper on the C1 and C2 domains of factor V.
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| 15. |
- Baumgartner, Stefan, et al.
(författare)
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The impact of the stone age diet on gingival conditions in the absence of oral hygiene.
- 2009
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Ingår i: Journal of Periodontology. - 0022-3492 .- 1943-3670. ; 80:5, s. 759-768
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of this study was to assess the oral microbiota and clinical data in subjects without access to traditional oral hygiene methods and who ate a diet available in the Stone Age.METHODS: Ten subjects living in an environment replicating the Stone Age for 4 weeks were enrolled in this study. Bleeding on probing (BOP), gingival and plaque indices, and probing depth (PD) were assessed at baseline and at 4 weeks. Microbiologic samples were collected at the mesio-buccal subgingival aspects of all teeth and from the dorsum of the tongue and were processed by checkerboard DNA-DNA hybridization methods.RESULTS: No subject had periodontitis. Mean BOP decreased from 34.8% to 12.6% (P <0.001). Mean gingival index scores changed from 0.38 to 0.43 (not statistically significant) and mean plaque scores increased from 0.68 to 1.47 (P <0.001). PD at sites of subgingival sampling decreased (mean difference: 0.2 mm; P <0.001). At week 4, the total bacterial count was higher (P <0.001) for 24 of 74 species, including Bacteroides ureolyticus, Eikenella corrodens, Lactobacillus acidophilus, Capnocytophaga ochracea, Escherichia coli, Fusobacterium nucleatum naviforme, Haemophilus influenzae, Helicobacter pylori, Porphyromonas endodontalis, Staphylococcus aureus (two strains), Streptococcus agalactiae, Streptococcus anginosis, and Streptococcus mitis. Bacterial counts from tongue samples were higher at baseline (P <0.001) for 20 species, including Tannerella forsythia (previously T. forsythensis), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; serotype a), and Streptococcus spp.CONCLUSIONS: The experimental gingivitis protocol is not applicable if the diet (e.g., Stone Age) does not include refined sugars. Although plaque levels increased, BOP and PD decreased. Subgingival bacterial counts increased for several species not linked to periodontitis, whereas tongue bacterial samples decreased during the study period.
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| 16. |
- Blechert, Oliver, et al.
(författare)
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Conserved function of the Krüppel gap gene in the blowfly Lucilia sericata, despite anterior shift of expression.
- 2011
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Ingår i: Insect Molecular Biology. - : Wiley. - 1365-2583 .- 0962-1075. ; 20, s. 257-265
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether expression patterns of segmentation genes found in Drosophila melanogaster can be scaled to pattern larger insects, we studied the expression of the Krüppel (Kr) gene in the blowfly Lucilia sericata. Compared with Drosophila Kr, L. sericata Kr showed an unexpected 10% shift of expression towards the anterior pole. Furthermore, expression domains not found in D. melanogaster were present at the blastoderm stage of L. sericata. To compare Kr activity and function, we employed RNA interference-mediated gene silencing. We found Kr phenotypes in L. sericata comparable with those observed in D. melanogaster, demonstrating that L. sericata Kr functions as a gap gene as it does in Drosophila. Our results show that, despite an anterior shift in expression, Kr function has remained conserved during the evolution of the blowflies.
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| 17. |
- Broadie, Kendal, et al.
(författare)
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Extracellular Matrix and Its Receptors in Drosophila Neural Development
- 2011
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Ingår i: Developmental Neurobiology. - : Wiley. - 1932-846X .- 1932-8451. ; 71:11, s. 1102-1130
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular matrix (ECM) and matrix receptors are intimately involved in most biological processes. The ECM plays fundamental developmental and physiological roles in health and disease, including processes underlying the development, maintenance, and regeneration of the nervous system. To understand the principles of ECM-mediated functions in the nervous system, genetic model organisms like Drosophila provide simple, malleable, and powerful experimental platforms. This article provides an overview of ECM proteins and receptors in Drosophila. It then focuses on their roles during three progressive phases of neural development: (1) neural progenitor proliferation, (2) axonal growth and pathfinding, and (3) synapse formation and function. Each section highlights known ECM and ECM-receptor components and recent studies done in mutant conditions to reveal their in vivo functions, all illustrating the enormous opportunities provided when merging work on the nervous system with systematic research into ECM-related gene functions. (C) 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 1102-1130, 2011
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| 18. |
- Cai, Xiaoli, et al.
(författare)
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bicoid RNA localization requires the trans-Golgi network
- 2019
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 156
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The formation of the bicoid (bcd) mRNA gradient is a crucial step for Bcd protein gradient formation in Drosophila. In the past, a microtubule (MT)-based cortical network had been shown to be indispensable for bcd mRNA transport to the posterior.Results: We report the identification of a MT-binding protein CLASP/Chb as the first component associated with this cortical MT network. Since CLASPs in vertebrates were shown to serve as an acentriolar microtubule organization center (aMTOC) in concert with trans-Golgi proteins, we examined the effect of the Drosophila trans-Golgins on bcd localization and gradient formation. Using a genetic approach, we demonstrate that the Drosophila trans-Golgins dGCC88, dGolgin97 and dGCC185 indeed affect bcd mRNA localization during oocyte development. Consequently, the bcd mRNA is already mislocalized before the egg is fertilized. The expression domains of genes downstream of the hierarchy of bcd, e.g. of the gap gene empty spiracles or of the pair-rule gene even-skipped are changed, indicating an altered segmental anlagen, due to a faulty bcd gradient. Thus, at the end of embryogenesis, trans-Golgin mutants show bcd-like cuticle phenotypes.Conclusions: Our data provides evidence that the Golgi as a cellular member of the secretory pathway exerts control on bcd localization which indicates that bcd gradient formation is probably more intricate than previously presumed.
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| 19. |
- Cai, Xiaoli, et al.
(författare)
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Cortical movement of Bicoid in early Drosophila embryos is actin- and microtubule-dependent and disagrees with the SDD diffusion model
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- The Bicoid (Bcd) protein gradient in Drosophila serves as a paradigm for gradient formation in textbooks. The SDD model (synthesis, diffusion, degradation) was proposed to explain the formation of the gradient. The SDD model states that the bcd mRNA is located at the anterior pole of the embryo at all times and serves a source for translation of the Bicoid protein, coupled with diffusion and uniform degradation throughout the embryo. Recently, the ARTS model (active RNA transport, synthesis) challenged the SDD model. In this model, the mRNA is transported at the cortex along microtubules to form a mRNA gradient which serves as template for the production of Bcd, hence little Bcd movement is involved. To test the validity of the SDD model, we developed a sensitive assay to monitor the movement of Bcd during early nuclear cycles. We observed that Bcd moved along the cortex and not in a broad front towards the posterior as the SDD model would have predicted. We subjected embryos to hypoxia where the mRNA remained strictly located at the tip at all times, while the protein was allowed to move freely, thus conforming to an ideal experimental setup to test the SDD model. Unexpectedly, Bcd still moved along the cortex. Moreover, cortical Bcd movement was sparse, even under longer hypoxic conditions. Hypoxic embryos treated with drugs compromising microtubule and actin function affected Bcd cortical movement and stability. Vinblastine treatment allowed the simulation of an ideal SDD model whereby the protein moved throughout the embryo in a broad front. In unfertilized embryos, the Bcd protein followed the mRNA which itself was transported into the interior of the embryo utilizing a hitherto undiscovered microtubular network. Our data suggest that the Bcd gradient formation is probably more complex than previously anticipated.
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| 20. |
- Cai, Xiaoli, et al.
(författare)
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Modulating the bicoid gradient in space and time
- 2021
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Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 158, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The formation of the Bicoid (Bcd) gradient in the early Drosophila is one of the most fascinating observations in biology and serves as a paradigm for gradient formation, yet its mechanism is still not fully understood. Two distinct models were proposed in the past, the SDD and the ARTS model.Results: We define novel cis- and trans-acting factors that are indispensable for gradient formation. The first one is the poly A tail length of the bcd mRNA where we demonstrate that it changes not only in time, but also in space. We show that posterior bcd mRNAs possess a longer poly tail than anterior ones and this elongation is likely mediated by wispy (wisp), a poly A polymerase. Consequently, modulating the activity of Wisp results in changes of the Bcd gradient, in controlling downstream targets such as the gap and pair-rule genes, and also in influencing the cuticular pattern. Attempts to modulate the Bcd gradient by subjecting the egg to an extra nuclear cycle, i.e. a 15th nuclear cycle by means of the maternal haploid (mh) mutation showed no effect, neither on the appearance of the gradient nor on the control of downstream target. This suggests that the segmental anlagen are determined during the first 14 nuclear cycles. Finally, we identify the Cyclin B (CycB) gene as a trans-acting factor that modulates the movement of Bcd such that Bcd movement is allowed to move through the interior of the egg.Conclusions: Our analysis demonstrates that Bcd gradient formation is far more complex than previously thought requiring a revision of the models of how the gradient is formed.
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| 21. |
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| 22. |
- Castillejo-Lopez, Casimiro, et al.
(författare)
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Drosophila exoribonuclease nibbler is a tumor suppressor, acts within the RNA(i) machinery and is not enriched in the nuage during early oogenesis
- 2017
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Ingår i: Hereditas. - : BIOMED CENTRAL LTD. - 0018-0661 .- 1601-5223. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Background: micro RNAs (miRNAs) are important regulators of many biological pathways. A plethora of steps are required to form, from a precursor, the mature miRNA that eventually acts on its target RNA to repress its expression or to inhibit translation. Recently, Drosophila nibbler (nbr) has been shown to be an important player in the maturation process of miRNA and piRNA. Nbr is an exoribonuclease which helps to shape the 3' end of miRNAs by trimming the 3' overhang to a final length. Results: In contrast to previous reports on the localization of Nbr, we report that 1) Nbr is expressed only during a short time of oogenesis and appears ubiquitously localized within oocytes, and that 2) Nbr was is not enriched in the nuage where it was shown to be involved in piwi-mediated mechanisms. To date, there is little information available on the function of nbr for cellular and developmental processes. Due to the fact that nbr mutants are viable with minor deleterious effects, we used the GAL4/UAS over-expression system to define novel functions of nbr. We disclose hitherto unknown functions of nbr 1) as a tumor suppressor and 2) as a suppressor of RNAi. Finally, we confirm that nbr is a suppressor of transposon activity. Conclusions: Our data suggest that nbr exerts much more widespread functions than previously reported from trimming 3' ends of miRNAs only.
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| 23. |
- Castillejo-Lopez, Casimiro, et al.
(författare)
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The fat-like gene of drosophila is the true orthologue of vertebrate fat cadherins and is involved in the formation of tubular organs.
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:23, s. 24034-24043
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Tidskriftsartikel (refereegranskat)abstract
- Fat cadherins constitute a subclass of the large cadherin family characterized by the presence of 34 cadherin motifs. To date, three mammalian Fat cadherins have been described; however, only limited information is known about the function of these molecules. In this paper, we describe the second fat cadherin in Drosophila, fat-like (ftl). We show that ftl is the true orthologue of vertebrate fat-like genes, whereas the previously characterized tumor suppressor cadherin, fat, is more distantly related as compared with ftl. Ftl is a large molecule of 4705 amino acids. It is expressed apically in luminal tissues such as trachea, salivary glands, proventriculus, and hindgut. Silencing of ftl results in the collapse of tracheal epithelia giving rise to breaks, deletions, and sac-like structures. Other tubular organs such as proventriculus, salivary glands, and hindgut are also malformed or missing. These data suggest that Ftl is required for morphogenesis and maintenance of tubular structures of ectodermal origin and underline its similarity in function to a reported lethal mouse knock-out of fat1 where glomerular epithelial processes collapse. Based on our results, we propose a model where Ftl acts as a spacer to keep tubular epithelia apart rather than the previously described adhesive properties of the cadherin superfamily.
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| 24. |
- Connolly, Stuart J., et al.
(författare)
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The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
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Tidskriftsartikel (refereegranskat)abstract
- Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
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| 25. |
- Deng, Wu-Min, et al.
(författare)
-
Dystroglycan is required for polarizing the epithelial cells and the oocyte in Drosophila.
- 2003
-
Ingår i: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 130:1, s. 173-184
-
Tidskriftsartikel (refereegranskat)abstract
- The transmembrane protein Dystroglycan is a central element of the dystrophin-associated glycoprotein complex, which is involved in the pathogenesis of many forms of muscular dystrophy. Dystroglycan is a receptor for multiple extracellular matrix (ECM) molecules such as Laminin, agrin and perlecan, and plays a role in linking the ECM to the actin cytoskeleton; however, how these interactions are regulated and their basic cellular functions are poorly understood. Using mosaic analysis and RNAi in the model organism Drosophila melanogaster, we show that Dystroglycan is required cell-autonomously for cellular polarity in two different cell types, the epithelial cells (apicobasal polarity) and the oocyte (anteroposterior polarity). Loss of Dystroglycan function in follicle and disc epithelia results in expansion of apical markers to the basal side of cells and overexpression results in a reduced apical localization of these same markers. In Dystroglycan germline clones early oocyte polarity markers fail to be localized to the posterior, and oocyte cortical F-actin organization is abnormal. Dystroglycan is also required non-cell-autonomously to organize the planar polarity of basal actin in follicle cells, possibly by organizing the Laminin ECM. These data suggest that the primary function of Dystroglycan in oogenesis is to organize cellular polarity; and this study sets the stage for analyzing the Dystroglycan complex by using the power of Drosophila molecular genetics.
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| 26. |
- Fahmy, Khalid, et al.
(författare)
-
Expression analysis of a family of developmentally-regulated cytosolic sulfotransferases (SULTs) in Drosophila.
- 2013
-
Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223 .- 0018-0661. ; 150:2-3, s. 44-48
-
Tidskriftsartikel (refereegranskat)abstract
- We have compared the amino acid sequence of all four cytosolic sulfotransferases (SULTs) in Drosophila and analyzed their spatial expression patterns during development. Three out of four SULTs show distinct expression activity during embryogenesis, while the 4th SULT shows expression only post-embryonically. st1, st3 and st4 are expressed in non-overlapping expression domains mainly confined to organs of the alimentary canal such as esophagus, malphigian tubules, hindgut, as well as in the tracheal system. All these organs are surrounded by the hemolymph suggesting that Drosophila SULTs exert their function in detoxification of substances upon influx from the hemolymph.
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| 27. |
- Fahmy, Khalid, et al.
(författare)
-
αTubulin 67C and Ncd Are Essential for Establishing a Cortical Microtubular Network and Formation of the Bicoid mRNA Gradient in Drosophila.
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
-
Tidskriftsartikel (refereegranskat)abstract
- The Bicoid (Bcd) protein gradient in Drosophila serves as a paradigm for gradient formation in textbooks. To explain the generation of the gradient, the ARTS model, which is based on the observation of a bcd mRNA gradient, proposes that the bcd mRNA, localized at the anterior pole at fertilization, migrates along microtubules (MTs) at the cortex to the posterior to form a bcd mRNA gradient which is translated to form a protein gradient. To fulfil the criteria of the ARTS model, an early cortical MT network is thus a prerequisite. We report hitherto undiscovered MT activities in the early embryo important for bcd mRNA transport: (i) an early and omnidirectional MT network exclusively at the anterior cortex of early nuclear cycle embryos showing activity during metaphase and anaphase only, (ii) long MTs up to 50 µm extending into the yolk at blastoderm stage to enable basal-apical transport. The cortical MT network is not anchored to the actin cytoskeleton. The posterior transport of the mRNA via the cortical MT network critically depends on maternally-expressed αTubulin67C and the minus-end motor Ncd. In either mutant, cortical transport of the bcd mRNA does not take place and the mRNA migrates along another yet undisclosed interior MT network, instead. Our data strongly corroborate the ARTS model and explain the occurrence of the bcd mRNA gradient.
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| 28. |
- Fascetti, Nora, et al.
(författare)
-
Expression of Drosophila Ten-a, a dimeric receptor during embryonic development.
- 2002
-
Ingår i: Mechanisms of Development. - 0925-4773. ; 114:1-2, s. 197-200
-
Tidskriftsartikel (refereegranskat)abstract
- Ten-a and Ten-m are the two Drosophila members of the newly discovered Ten-m family of dimeric type II transmembrane proteins. Here, we report complete cDNA cloning and protein expression patterns of Ten-a. The Ten-a protein, a dimeric receptor of about 500 kDa is mainly expressed on axons of the embryonic central nervous system and on muscle attachment sites.
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| 29. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 30. |
- Friedrich, Martin V K, et al.
(författare)
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Perlecan domain V of Drosophila melanogaster : Sequence, recombinant analysis and tissue expression
- 2000
-
Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956. ; 267:11, s. 3149-3159
-
Tidskriftsartikel (refereegranskat)abstract
- The C-terminal domain V of the basement membrane proteoglycan perlecan was previously shown to play a major role in extracellular matrix and cell interactions. A homologous sequence of 708 amino-acid residues from Drosophila has now been shown to be 33% identical to mouse perlecan domain V. It consists of three laminin G-type (LG) and epidermal growth factor-like (EG) modules but lacks the EG3 module and a link region found in mammalian perlecans. Recombinant production of Drosophila perlecan domain V in mammalian cells yielded a 100-kDa protein which was folded into a linear array of three globular LG domains. Unlike the mouse counterpart, domain V from Drosophila was not modified by glycosaminoglycans and endogenous proteolysis, due to the absence of the link region. It showed moderate affinities for heparin and sulfatides but did not bind to chick α- dystroglycan or to various mammalian basement membrane proteins. A single RGD sequence in LG3 of Drosophila domain V was also incapable of mediating cell adhesion. Production of a proteoglycan form of perlecan (≃ 450 kDa) in one Drosophila cell line could be demonstrated by immunoblotting with antibodies against Drosophila domain V. A strong expression was also found by in situ hybridization and immunohistology at various stages of embryonic development and expression was localized to several basement membrane zones. This indicates, as for mammalian species, a distinct role of perlecan during Drosophila development.
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| 31. |
- Gilg, Stefan, et al.
(författare)
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Molecular adsorbent recirculating system treatment in patients with post-hepatectomy liver failure : Long-term results of a pilot study
- 2022
-
Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 111:3, s. 48-55
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort.Methods: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria.Results: The cohort was split into three time periods: pre-MARS period (n = 192), MARS study period (n = 207), and post-MARS period (n = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period (p = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3–51.7) in the pre-MARS cohort, 57 months (40.7–75.6) in the MARS cohort, and 38.8 months (31.4–51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5–25.9), respectively (p = 0.138)).Conclusions: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed.The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).
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| 32. |
- Graner, Michael W., et al.
(författare)
-
Splice variants of the Drosophila PS2 integrins differentially interact with RGD-containing fragments of the extracellular proteins tiggrin, Ten-m, and D-laminin α2
- 1998
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 273:29, s. 18235-18241
-
Tidskriftsartikel (refereegranskat)abstract
- Two new potential ligands of the Drosophila PS2 integrins have been characterized by functional interaction in cell culture. These potential ligands are a new Drosophila laminin α2 chain encoded by the wing blister locus and Ten-m, an extracellular protein known to be involved in embryonic pattern formation. As with previously identified PS2 ligands, both contain RGD sequences, and RGD-containing fragments of these two proteins (DLAM-RGD and TENM-RGD) can support PS2 integrin-mediated cell spreading. In all cases, this spreading is inhibited specifically by short RGD-containing peptides. As previously found for the PS2 ligand tiggrin (and the tiggrin fragment TIG- RGD), TENM-RGD induces maximal spreading of cells expressing integrin containing the α(PS2C) splice variant. This is in contrast to DLAM-RGD, which is the first Drosophila polypeptide shown to interact preferentially with cells expressing the α(PS2) (M8) splice variant. The β(PS) integrin subunit also varies in the presumed ligand binding region as a result of alternative splicing. For TIG-RGD and TENM-RGD, the β splice variant has little effect, but for DLAM-RGD, maximal cell spreading is supported only by the β(PS4A) form of the protein. Thus, the diversity in PS2 integrins due to splicing variations, in combination with diversity of matrix ligands, can greatly enhance the functional complexity of PS2-ligand interactions in the developing animal. The data also suggest that the Splice variants may alter regions of the subunits that are directly involved in ligand interactions, and this is discussed with respect to models of integrin structure.
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| 33. |
- Graner, Michael W., et al.
(författare)
-
Splice variants of the Drosophila PS2 integrins differentially interact with the extracellular ligands Tiggrin, D-laminin alpha 2 and Ten-m.
- 1998
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 273:29, s. 18235-18241
-
Tidskriftsartikel (refereegranskat)abstract
- Two new potential ligands of theDrosophila PS2 integrins have been characterized by functional interaction in cell culture. These potential ligands are a new Drosophila laminin α2 chain encoded by the wing blister locus and Ten-m, an extracellular protein known to be involved in embryonic pattern formation. As with previously identified PS2 ligands, both contain RGD sequences, and RGD-containing fragments of these two proteins (DLAM-RGD and TENM-RGD) can support PS2 integrin-mediated cell spreading. In all cases, this spreading is inhibited specifically by short RGD-containing peptides. As previously found for the PS2 ligand tiggrin (and the tiggrin fragment TIG-RGD), TENM-RGD induces maximal spreading of cells expressing integrin containing the αPS2C splice variant. This is in contrast to DLAM-RGD, which is the first Drosophila polypeptide shown to interact preferentially with cells expressing the αPS2 m8 splice variant. The βPS integrin subunit also varies in the presumed ligand binding region as a result of alternative splicing. For TIG-RGD and TENM-RGD, the β splice variant has little effect, but for DLAM-RGD, maximal cell spreading is supported only by the βPS4A form of the protein. Thus, the diversity in PS2 integrins due to splicing variations, in combination with diversity of matrix ligands, can greatly enhance the functional complexity of PS2-ligand interactions in the developing animal. The data also suggest that the splice variants may alter regions of the subunits that are directly involved in ligand interactions, and this is discussed with respect to models of integrin structure.
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| 34. |
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| 35. |
- Hunding, Axel, et al.
(författare)
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Ancient role of ten-m/odz in segmentation and the transition from sequential to syncytial segmentation
- 2017
-
Ingår i: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 154
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Until recently, mechanisms of segmentation established for Drosophila served as a paradigm for arthropod segmentation. However, with the discovery of gene expression waves in vertebrate segmentation, another paradigm based on oscillations linked to axial growth was established. The Notch pathway and hairy delay oscillator are basic components of this mechanism, as is the wnt pathway. With the establishment of oscillations during segmentation of the beetle Tribolium, a common segmentation mechanism may have been present in the last common ancestor of vertebrates and arthropods. However, the Notch pathway is not involved in segmentation of the initial Drosophila embryo. In arthropods, the engrailed, wingless pair has a much more conserved function in segmentation than most of the hierarchy established for Drosophila.RESULTS: Here, we work backwards from this conserved pair by discussing possible mechanisms which could have taken over the role of the Notch pathway. We propose a pivotal role for the large transmembrane protein Ten-m/Odz. Ten-m/Odz may have had an ancient role in cell-cell communication, parallel to the Notch and wnt pathways. The Ten-m protein binds to the membrane with properties which resemble other membrane-based biochemical oscillators.CONCLUSION: We propose that such a simple transition could have formed the initial scaffold, on top of which the hierarchy, observed in the syncytium of dipterans, could have evolved.
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| 36. |
- Höltinger, Stefan, et al.
(författare)
-
The impact of climatic extreme events on the feasibility of fully renewable power systems : a case study for Sweden
- 2019
-
Ingår i: Energy. - : Elsevier. - 0360-5442 .- 1873-6785. ; 178, s. 695-713
-
Tidskriftsartikel (refereegranskat)abstract
- Long term time series of variable renewable energy (VRE) generation and electricity demand (load) provide important insights into the feasibility of fully renewable power systems. The coverage of energy statistics is usually too short or the temporal resolution too low to study effects related to interannual variability or the impact of climatic extreme events. We use time series simulated from climate data to assess the frequency, duration, and magnitude of extreme residual load events of two fully renewable power scenarios with a share of VRE generation (wind and solar PV) of about 50% for the case of Sweden. We define residual load as load – wind – PV – nuclear generation. Extreme residual load events are events that exceed the balancing or ramping capacities of the current power system. For our analysis, we use 29 years of simulated river runoff and wind and PV generation. Hourly load is derived from MERRA reanalysis temperature data by applying statistical models. Those time series are used along with historic capacity and ramping restrictions of hydro and thermal power plants in an optimization model to minimize extreme residual load events. Our analysis shows that even highly flexible power systems, as the Swedish one, are affected by climatic extreme events if they increase their VRE shares. Replacing current nuclear power capacities by wind power results on average in three extreme residual load events per year that exceed the current power system’s flexibility. Additional PV generation capacities instead of wind increase the number of extreme residual load events by about 4 %, as most events occur during the winter month when solar generation is close to zero and thus not able to counterbalance low wind events. Contrarily, overproduction and the need to curtail VRE generation become more pressing with higher shares of PV. In the discussion we highlight measures that could provide additional balancing capabilities to cope with the more frequent and severe residual load events in a fully renewable power system with high shares of VRE generation.
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| 37. |
- Khalili, Dilan, et al.
(författare)
-
Anti-Fibrotic Activity of an Antimicrobial Peptide in a Drosophila Model
- 2021
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 13:6, s. 376-390
-
Tidskriftsartikel (refereegranskat)abstract
- Fibrotic lesions accompany several pathological conditions, including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components, including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apicobasal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide drosomycin (Drs), which also restores the secretory activity of the SGs. In addition to extracellular matrix components, both Drs and F-actin localize to fibrotic lesions.
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| 38. |
- Khare, Narmada, et al.
(författare)
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Dally-like protein, a new Drosophila glypican with expression overlapping with wingless
- 2000
-
Ingår i: Mechanisms of Development. - 0925-4773. ; 99:1-2, s. 199-202
-
Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans, the molecules of extracellular matrix, carry a highly negative charge due to their glycosaminoglycan (GAG) chains and large volumes. They were considered to play a secondary role in activities like cell division, adhesion, blood coagulation, etc. until the importance of their sugar chains in the fibroblast growth factor (FGF) signalling was discovered (Science 252 (1991) 1705; Cell 64 (1991) 841). Studies of mutations in the genes sugarless(sgl) and sulfateless (sfl) have proved that the proteoglycans involved in Wg signalling contain heparan sulfate GAG chains (Development 124 (1997) 2623; Development 124 (1997) 3055; Development 124 (1997) 3565; Development 126 (1999) 3715). This has led to the attribution of specific functions to these molecules (J. Cell Biol. 148 (2000) 227). The Glypican family of heparan sulfate proteoglycans (HSPGs) is characterized by core proteins with conserved cysteine residues and attachment to the cell surface by a glycosylphosphatidyl inositol (GPI) anchor. This may lead to endocytic pathways that are different from other HSPGs, higher lateral mobility and possible apical localisation in a cell (Proc. Natl. Acad. Sci, USA 85 (1988) 9557). Variations in their HS contents may effect binding properties and localisation (J. Cell Biol. 124 (1994) 149; J. Cell Biol. 132 (1996) 487), thus specialising each member for a unique biological function. Glypicans play important roles in morphogenetic pathways, e.g. human glypican 3 (GPC3) is mutated in Simpson-Golabi-Behmel syndrome making an individual prone to tumours (Nat. Genet. 12 (1996) 241). Dally, the first Drosophila member of the family, is essential for the wingless and decapentaplegic signalling pathways (Development 121 (1995) 3687; Development 124 (1997) 4113). Here, we report a new Drosophila glypican, dally-like protein (dlp) with all the features of a glypican. Based on expression studies we report its colocalisation with Wg. (C) 2000 Elsevier Science Ireland Ltd.
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| 39. |
- Khare, Narmada, et al.
(författare)
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Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis
- 2000
-
Ingår i: Mechanisms of Development. - 0925-4773. ; 91:08-01-02, s. 393-397
-
Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and expression analysis of two new Drosophila members of the Semaphorin family. Both proteins show the presence of Semaphorin domains and transmembrane domains. Both genes are expressed maternally and in embryos, and reveal distinct expression patterns much earlier than the onset of neurogenesis. We also present an overview of the domain structure of all so far known semaphorins in Drosophila. Furthermore, we compared all Drosophila and C. elegans Semaphorins and discuss them in the light of their evolution.
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| 40. |
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| 41. |
- Martin, Doris, et al.
(författare)
-
wing blister, A new Drosophila laminin alpha chain required for cell adhesion and migration during embryonic and imaginal development
- 1999
-
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 145:1, s. 191-201
-
Tidskriftsartikel (refereegranskat)abstract
- We report the molecular and functional characterization of a new α chain of laminin in Drosophila. The new laminin chain appears to be the Drosophila counterpart of both vertebrate α2 (also called merosin) and α1 chains, with a slightly higher degree of homology to α2, suggesting that this chain is an ancestral version of both αl and α2 chains. During embryogenesis, the protein is associated with basement membranes of the digestive system and muscle attachment sites, and during larval stage it is found in a specific pattern in wing and eye discs. The gene is assigned to a locus called wing blister (wb), which is essential for embryonic viability. Embryonic phenotypes include twisted germbands and fewer pericardial cells, resulting in gaps in the presumptive heart and tracheal trunks, and myotubes detached from their target muscle attachment sites. Most phenotypes are in common with those observed in Drosophila laminin α3, 5 mutant embryos and many are in common with those observed in integrin mutations. Adult phenotypes show blisters in the wings in viable allelic combinations, similar to phenotypes observed in integrin genes. Mutation analysis in the eye demonstrates a function in rhabdomere organization. In summary, this new laminin α chain is essential for embryonic viability and is involved in processes requiring cell migration and cell adhesion.
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| 42. |
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| 43. |
- Mellenthin, Katja, et al.
(författare)
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Wingless signaling in a large insect, the blowfly Lucilia sericata: A beautiful example of evolutionary developmental biology
- 2006
-
Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 235:2, s. 347-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blowflies are the primary facultative agent in causing myiasis of domestic sheep in the whole world and, at the same time, it is an important tool for forensic medicine. Surprisingly, and in contrast to its importance, almost no data regarding the embryology and molecular markers are known for this insect. In this report, we present a detailed description of the blowfly Lucilia sericata embryogenesis and of imaginal disc development. The embryogenesis of Lucilia strongly resembles that of Drosophila, despite their apparent size difference. Moreover, imaginal disc development appears to be equally well conserved. Through cloning, expression, and functional studies, we show that the Lucilia Wingless (Wg) protein is highly conserved between the two species. We further show that parasegments are established in Lucilia, however, engrailed expression shows a more dynamic expression pattern than expected in comparison to Drosophila. Over-expression of Lucilia Wingless in Drosophila shows wingless-like wing phenotypes, suggesting that Lucilia Wingless blocks the signalling activity of Drosophila Wingless. Upon injection of wg dsRNA, we observe a "lawn of denticle" phenotype, closely resembling that of Drosophila. Due to the large size of the insect, the distance over which Wingless exerts signalling activity is up to three times larger than in Drosophila, yet the consequences are very similar. Our data demonstrate long-range wingless signaling mechanisms adapted for patterning large domains of naked cuticle and suggest signaling properties of Lucilia Wingless that are distinct from those of Drosophila Wingless.
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| 44. |
- Minet, Ariane D., et al.
(författare)
-
Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain
- 1999
-
Ingår i: Journal of Cell Science. - 0021-9533. ; 112:12, s. 2019-2032
-
Tidskriftsartikel (refereegranskat)abstract
- The Drosophila gene ten-m is the first pair-rule gene not encoding a transcription factor, but an extracellular protein. We have characterized a highly conserved chicken homologue that we call teneurin-1. The C-terminal part harbors 26 repetitive sequence motifs termed YD-repeats. The YD-repeats are most similar to the core of the rhs elements of Escherichia coli. Related repeats in toxin A of Clostridium difficile are known to bind specific carbohydrates. We show that recombinantly expressed proteins containing the YD-repeats of teneurin-1 bind to heparin. Furthermore, heparin lyase treatment of extracts of cells expressing recombinant YD-repeat protein releases this protein from high molecular mass aggregates. In situ hybridization and immunostaining reveals teneurin-1 expression in neurons of the developing visual system of chicken and Drosophila. This phylogenetic conservation of neuronal expression from flies to birds implies fundamental roles for teneurin-1 in neurogenesis. This is supported by the neurite outgrowth occurring on substrates made of recombinant YD-repeat proteins, which can be inhibited by heparin. Database searches resulted in the identification of ESTs encoding at least three further members of the teneurin family of proteins. Furthermore, the human teneurin-1 gene could be identified on chromosome Xq24/25, a region implied in an X-linked mental retardation syndrome.
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| 45. |
- Ngernsiri, Lertluk, et al.
(författare)
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Preliminary studies on the role of ten-a during CNS and eye development of Drosophila.
- 2005
-
Ingår i: ScienceAsia. - 1513-1874. ; 31, s. 5-11
-
Tidskriftsartikel (refereegranskat)abstract
- ten-a is one of the two Drosophila genes whose products belong to the Ten M protein family. TheTen-a protein is a type II transmembrane protein. This protein was found to be mainly expressed in the CNSof the embryo and in the compound eye of the pupa. No report about the function of ten-a has beenpublished to date. Here, we showed, in a preliminary report, that ten-a has a function in the development ofthe CNS and in the compound eye. To study the function of ten-a during CNS development, doublestranded RNA interference (dsRNAi) experiments were performed. We found that embryos without Ten-aprotein have defects in the commissures, suggesting that ten-a is likely to be involved in commissureformation. Furthermore, to study the function of ten-a in the eye, the Gal4/UAS system was used tooverexpress ten-a at different stages of eye development. We found that extra amounts of Ten-a can interferewith the development of the eye. Flies overexpressing ten-a showed eye defects such as small and rough eyes,and black ommatidia. The results indicated that ten-a may be a novel gene involved in eye morphogenesis
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| 46. |
- Ngernsiri, Lertluk, et al.
(författare)
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Ten-a overexpression causes abnormal pattern in the Drosophila compound eye
- 2006
-
Ingår i: Insect science. - : Wiley. - 1672-9609 .- 1744-7917. ; 13:5, s. 355-364
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Ten-a is one of the two Drosophila proteins that belong to the Ten M protein family. This protein is a type II transmembrane protein and is expressed mainly in the embryonic CNS, in the larval eye imaginal disc and in the compound eye of the pupa. Here, we investigate the role of ten-a during development of the compound eye by using the Gal4/UAS system to induce ten-a overexpression in the developing eye. We found that overexpression of ten-a can perturb eye development during all stages examined. In an early stage, overexpression of ten-a in eye primordial cells caused small and rough eyes and interfered with photoreceptor cell recruitment, resulting in some ommatidia having fewer or extra photoreceptor cells. Conversely, ten-a overexpression during ommatidial formation caused severe eye defects due to absence of many cellular components. Interestingly, overexpression of ten-a in the late stage developing ommatidial cluster affected the number of pigment cells, caused cone cells proliferation in many ommatidia, and caused some photoreceptor cell defects. These results suggest that ten-a may be a novel gene required for normal eye morphogenesis.
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| 47. |
- Rietschel, Liz, et al.
(författare)
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Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes.
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
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| 48. |
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| 49. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 50. |
- Schneider, Martina, et al.
(författare)
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Differential expression of Dystroglycan-spliceforms with and without the mucin-like domain during Drosophila embryogenesis
- 2008
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Ingår i: Fly. - 1933-6934. ; 2:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Dystroglycan (DG) is a widely expressed extracellular matrix (ECM) receptor required for muscle viability, synaptogenesis, basement-membrane formation and epithelial development. As an integral component of the Dystrophin-associated glycoprotein complex, DG plays a central role in linking the ECM and the cytoskeleton. Disruption of this linkage in skeletal muscle is the underlying cause in various types of muscular dystrophies (MD). One particular type of MD is caused by alterations of O-linked glycosylation in the mucin-like domain of DG, which is required for binding of the ECM molecules Laminin and Perlecan. In epithelial cells, reduced expression of DG is associated with increased invasiveness of cancer cells and loss of cell polarity. Drosophila Dg is, in contrast to vertebrate Dg, subjected to differential splicing of the mRNA. Interestingly, the shorter DG splice forms lack the mucin-like domain. Here, we describe the embryonic expression patterns of full-length DG and a short variant of DG. We find that differential splicing of Dg is developmentally regulated and tissue-specific. In some tissues, e. g., hindgut, midgut constrictions, gonads, both DG variants can be detected. For the long form, we detected specific expression at the blastoderm stage, in the epidermis and in the tracheal pits. The short form showed exclusive expression in dorsal vessel cells, chordotonal organs and dorsal median cells. In the nervous system, the long form is predominantly expressed on axons, while the short form is present on glial cells. Our findings further support the idea that DG forms lacking the mucin-like domain serve a specific function in Drosophila.
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