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- Allan, Douglas W, et al.
(författare)
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Specification of Neuropeptide Cell Identity by the Integration of Retrograde BMP Signaling and a Combinatorial Transcription Factor Code
- 2003
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Ingår i: Cell. - Cambridge, United States : Cell Press. - 0092-8674 .- 1097-4172. ; 113:1, s. 73-86
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Tidskriftsartikel (refereegranskat)abstract
- Individual neurons express only one or a few of the many identified neurotransmitters and neuropeptides, but the molecular mechanisms controlling their selection are poorly understood. In the Drosophila ventral nerve cord, the six Tv neurons express the neuropeptide gene FMRFamide. Each Tv neuron resides within a neuronal cell group specified by the LIM-homeodomain gene apterous. We find that the zinc-finger gene squeeze acts in Tv cells to promote their unique axon pathfinding to a peripheral target. There, the BMP ligand Glass bottom boat activates the Wishful thinking receptor, initiating a retrograde BMP signal in the Tv neuron. This signal acts together with apterous and squeeze to activate FMRFamide expression. Reconstituting this "code," by combined BMP activation and apterous/squeeze misexpression, triggers ectopic FMRFamide expression in peptidergic neurons. Thus, an intrinsic transcription factor code integrates with an extrinsic retrograde signal to select a specific neuropeptide identity within peptidergic cells.
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| 4. |
- Billker, Oliver, et al.
(författare)
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Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite
- 2004
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 117:4, s. 503-514
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Tidskriftsartikel (refereegranskat)abstract
- Transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA). Using a Plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that XA triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their differentiation into gametes. A member of a family of plant-like calcium dependent protein kinases, CDPK4, is identified as the molecular switch that translates the XA-induced calcium signal into a cellular response by regulating cell cycle progression in the male gametocyte. CDPK4 is shown to be essential for the sexual reproduction and mosquito transmission of P. berghei. This study reveals an unexpected function for a plant-like signaling pathway in cell cycle regulation and life cycle progression of a malaria parasite.
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| 5. |
- Boström, Hans, et al.
(författare)
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PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.
- 1996
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 85:6, s. 863-73
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Tidskriftsartikel (refereegranskat)abstract
- A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.
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- Hurme, R, et al.
(författare)
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A proteinaceous gene regulatory thermometer in Salmonella
- 1997
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Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 90:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Novel utilization of the coiled-coil motif is presented that enables TlpA, an autoregulatory repressor protein in Salmonella, to sense temperature shifts directly and thereby to modulate the extent of transcription repression. Salmonella cells shifted to higher temperatures, such as those encountered at host entry, showed derepressed tlpA activity. tlpA::lacZ fusions indicated that the promoter itself is insensitive to thermal shifts and that transcription control was exerted by the autorepressor TlpA only. In vitro studies with highly purified TlpA showed concentration and temperature dependence for both fully folded conformation and function, indicating that the thermosensing in TlpA is based on monomer-to-coiled-coil equilibrium.
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| 20. |
- Robinson, Nicholas P., et al.
(författare)
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Identification of two origins of replication in the single chromosome of the archaeon Sulfolobus solfataricus
- 2004
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Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 116:1, s. 25-38
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Tidskriftsartikel (refereegranskat)abstract
- Eukaryotic chromosomes possess multiple origins of replication, whereas bacterial chromosomes are replicated from a single origin. The archaeon Pyrococcus abyssi also appears to have a single origin, suggesting a common rule for prokaryotes. However, in the current work, we describe the identification of two active origins of replication in the single chromosome of the hyperthermophilic archaeon Sulfolobus solfataricus. Further, we identify conserved sequence motifs within the origins that are recognized by a family of three Sulfolobus proteins that are homologous to the eukaryotic initiator proteins Orc1 and Cdc6. We demonstrate that the two origins are recognized by distinct subsets of these Orc1/Cdc6 homologs. These data, in conjunction with an analysis of the levels of the three Orc1/Cdc6 proteins in different growth phases and cell cycle stages, lead us to propose a model for the roles for these proteins in modulating origin activity.
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| 24. |
- Wahlgren, M, et al.
(författare)
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Waves of malarial var-iations
- 1999
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Ingår i: Cell. - 0092-8674. ; 96:5, s. 603-606
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Tidskriftsartikel (refereegranskat)
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| 25. |
- Wai, Sun Nyunt, et al.
(författare)
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Vesicle-mediated export and assembly of pore-forming oligomers of the enterobacterial ClyA cytotoxin.
- 2003
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Ingår i: Cell. - 0092-8674. ; 115:1, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- The ClyA protein is a pore-forming cytotoxin expressed by Escherichia coli and some other enterobacteria. It confers cytotoxic activity toward mammalian cells, but it has remained unknown how ClyA is surface exposed and exported from bacterial cells. Outer-membrane vesicles (OMVs) released from the bacteria were shown to contain ClyA protein. ClyA formed oligomeric pore assemblies in the OMVs, and the cytotoxic activity toward mammalian cells was considerably higher than that of ClyA protein purified from the bacterial periplasm. The redox status of ClyA correlated with its ability to form the oligomeric pore assemblies. In bacterial cells with a defective periplasmic disulphide oxidoreductase system, the ClyA protein was phenotypically expressed in a constitutive manner. The results define a vesicle-mediated transport mechanism in bacteria, and our findings show that the localization of proteins to OMVs directly may contribute to the activation and delivery of pathogenic effector proteins.
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