| 1. |
- Maier, Hannes, et al.
(author)
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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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In: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
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Journal article (peer-reviewed)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.
(author)
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Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
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Journal article (peer-reviewed)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.
(author)
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Locally rare species influence grassland ecosystem multifunctionality
- 2016
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In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Journal article (peer-reviewed)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.
(author)
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Characterisation of Drosophila thrombospondin defines an early origin of pentameric thrombospondins
- 2003
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In: Journal of Molecular Biology. - 1089-8638. ; 328:2, s. 479-494
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Journal article (peer-reviewed)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.
(author)
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Structural conservation of the salivary gland-specific slalom gene in the blowfly Lucilia sericata
- 2005
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In: Development, Genes and Evolution. - : Springer Science and Business Media LLC. - 0949-944X .- 1432-041X. ; 215:10, s. 537-543
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Journal article (peer-reviewed)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.
(author)
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Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless
- 2001
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In: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 128:1, s. 87-94
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Journal article (peer-reviewed)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.
(author)
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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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In: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:4
-
Journal article (peer-reviewed)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.
(author)
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Discovery of Teneurins
- 2019
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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 13, s. 1-9
-
Research review (peer-reviewed)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. |
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| 11. |
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| 12. |
- Baumgartner, Stefan
(author)
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Revisiting bicoid function : complete inactivation reveals an additional fundamental role in Drosophila egg geometry specification
- 2024
-
In: Hereditas. - 0018-0661. ; 161:1
-
Journal article (peer-reviewed)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
(author)
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Seeing is believing : the Bicoid protein reveals its path
- 2018
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In: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 155
-
Journal article (peer-reviewed)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.
(author)
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The discoidin domain family revisited : new members from prokaryotes and a homology-based fold prediction
- 1998
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In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 7:7, s. 31-1626
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of Periodontology. - 0022-3492 .- 1943-3670. ; 80:5, s. 759-768
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Journal article (peer-reviewed)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.
(author)
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Conserved function of the Krüppel gap gene in the blowfly Lucilia sericata, despite anterior shift of expression.
- 2011
-
In: Insect Molecular Biology. - : Wiley. - 1365-2583 .- 0962-1075. ; 20, s. 257-265
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Journal article (peer-reviewed)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.
(author)
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Extracellular Matrix and Its Receptors in Drosophila Neural Development
- 2011
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In: Developmental Neurobiology. - : Wiley. - 1932-846X .- 1932-8451. ; 71:11, s. 1102-1130
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Journal article (peer-reviewed)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.
(author)
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bicoid RNA localization requires the trans-Golgi network
- 2019
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In: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 156
-
Journal article (peer-reviewed)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.
(author)
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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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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
-
Journal article (peer-reviewed)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.
(author)
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Modulating the bicoid gradient in space and time
- 2021
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In: Hereditas. - : Springer Science and Business Media LLC. - 1601-5223. ; 158, s. 1-14
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Journal article (peer-reviewed)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.
(author)
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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
-
In: Hereditas. - : BIOMED CENTRAL LTD. - 0018-0661 .- 1601-5223. ; 155
-
Journal article (peer-reviewed)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.
(author)
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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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In: Journal of Biological Chemistry. - 1083-351X. ; 279:23, s. 24034-24043
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Journal article (peer-reviewed)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.
(author)
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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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In: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
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Journal article (peer-reviewed)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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- Deng, Wu-Min, et al.
(author)
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Dystroglycan is required for polarizing the epithelial cells and the oocyte in Drosophila.
- 2003
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In: Development: For advances in developmental biology and stem cells. - 1477-9129. ; 130:1, s. 173-184
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Journal article (peer-reviewed)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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