| 1. |
- Dong, X.-P., et al.
(författare)
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The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7215, s. 992-996
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Tidskriftsartikel (refereegranskat)abstract
- TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe3+-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe2+ transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe2+ transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe2+ permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe2+ at varying degrees, which correlate well with the disease severity. A comparison of TRPML1-/-ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe2+ levels, an increase in intralysosomal Fe 2+ levels and an accumulation of lipofuscin-like molecules in TRPML1-/- cells. We propose that TRPML1 mediates a mechanism by which Fe2+ is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients. ©2008 Macmillan Publishers Limited. All rights reserved.
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| 2. |
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| 3. |
- Hugot, J-P, et al.
(författare)
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Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
- 2001
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 411:6837, s. 599-603
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-?B, this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-?B in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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| 4. |
- Keeling, Linda, et al.
(författare)
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Chicken genomics : feather-pecking and victim pigmentation.
- 2004
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 431:7009
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Tidskriftsartikel (refereegranskat)abstract
- Feather-pecking in domestic birds is associated with cannibalism and severe welfare problems. It is a dramatic example of a spiteful behaviour in which the victim's fitness is reduced for no immediate direct benefit to the perpetrator and its evolution is unexplained. Here we show that the plumage pigmentation of a chicken may predispose it to become a victim: birds suffer more drastic feather-pecking when the colour of their plumage is due to the expression of a wild recessive allele at PMEL17, a gene that controls plumage melanization, and when these birds are relatively common in a flock. These findings, obtained using an intercross between a domestic fowl and its wild ancestor, have implications for the welfare of domestic species and offer insight into the genetic changes associated with the evolution of feather-pecking during the early stages of domestication.
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| 5. |
- Lundström, Ingemar
(författare)
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Artificial noses : Picture the smell
- 2000
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 406:6797, s. 682-683
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Forskningsöversikt (refereegranskat)
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| 6. |
- Pace, Michael L., et al.
(författare)
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Whole-lake carbon-13 additions reveal terrestrial support of aquatic food webs
- 2004
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 427:6971, s. 240-243
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystems are supported by organic carbon from two distinct sources. Endogenous carbon is produced by photosynthesis within an ecosystem by autotrophic organisms. Exogenous carbon is produced elsewhere and transported into ecosystems. Consumers may use exogenous carbon with consequent influences on population dynamics, predator-prey relationships and ecosystem processes(1). For example, exogenous inputs provide resources that may enhance consumer abundance beyond levels supported by within-system primary production(2). Exogenous fluxes of organic carbon to ecosystems are often large, but this material is recalcitrant and difficult to assimilate, in contrast to endogenously produced organic matter, which is used more easily(3,4). Here we show, by the experimental manipulation of dissolved inorganic C-13 in two lakes, that internal primary production is insufficient to support the food webs of these ecosystems. Additions of NaH (CO3)-C-13 enriched the C-13 content of dissolved inorganic carbon, particulate organic carbon, zooplankton and fish. Dynamics of C-13 indicate that 40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived from terrestrial sources, showing that there is significant subsidy of these ecosystems by organic carbon produced outside their boundaries.
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| 7. |
- Pizzari, Tommaso, et al.
(författare)
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Sophisticated sperm allocation in male fowl
- 2003
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 426:6962, s. 70-74
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Tidskriftsartikel (refereegranskat)abstract
- When a female is sexually promiscuous, the ejaculates of different males compete for the fertilization of her eggs; the more sperm a male inseminates into a female, the more likely he is to fertilize her eggs. Because sperm production is limited and costly, theory predicts that males will strategically allocate sperm (1) according to female promiscuity, (2) saving some for copulations with new females, and (3) to females producing more and/or better offspring. Whether males allocate sperm in all of these ways is not known, particularly in birds where the collection of natural ejaculates only recently became possible. Here we demonstrate male sperm allocation of unprecedented sophistication in the fowl Gallus gallus. Males show status-dependent sperm investment in females according to the level of female promiscuity; they progressively reduce sperm investment in a particular female but, on encountering a new female, instantaneously increase their sperm investment; and they preferentially allocate sperm to females with large sexual ornaments signalling superior maternal investment. Our results indicate that female promiscuity leads to the evolution of sophisticated male sexual behaviour.
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| 8. |
- Sandewall, Erik, 1945-
(författare)
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Systems - Opening up the process
- 2006
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 9. |
- Smits, Edsger C. P., et al.
(författare)
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Bottom-up organic integrated circuits
- 2008
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 455:7215, s. 956-959
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Tidskriftsartikel (refereegranskat)abstract
- Self- assembly - the autonomous organization of components into patterns and structures(1) - is a promising technology for the mass production of organic electronics. Making integrated circuits using a bottom- up approach involving self- assembling molecules was proposed(2) in the 1970s. The basic building block of such an integrated circuit is the self- assembled- monolayer field- effect transistor ( SAMFET), where the semiconductor is a monolayer spontaneously formed on the gate dielectric. In the SAMFETs fabricated so far, current modulation has only been observed in submicrometre channels(3-5), the lack of efficient charge transport in longer channels being due to defects and the limited intermolecular pi-pi coupling between the molecules in the self-assembled monolayers. Low field- effect carrier mobility, low yield and poor reproducibility have prohibited the realization of bottom- up integrated circuits. Here we demonstrate SAMFETs with long- range intermolecular pi - pi coupling in the monolayer. We achieve dense packing by using liquid- crystalline molecules consisting of a pi- conjugated mesogenic core separated by a long aliphatic chain from a monofunctionalized anchor group. The resulting SAMFETs exhibit a bulk- like carrier mobility, large current modulation and high reproducibility. As a first step towards functional circuits, we combine the SAMFETs into logic gates as inverters; the small parameter spread then allows us to combine the inverters into ring oscillators. We demonstrate real logic functionality by constructing a 15- bit code generator in which hundreds of SAMFETs are addressed simultaneously. Bridging the gap between discrete monolayer transistors and functional self-assembled integrated circuits puts bottom- up electronics in a new perspective.
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| 10. |
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