26 research outputs found

    Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1 genes

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    BACKGROUND: Despite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that the insulin-like growth factor (IGF) pathway has a central role in growth regulation, probably in all animals. The involvement of imprinted genes has also attracted much attention, not least because two of the earliest discovered were shown to be oppositely imprinted and antagonistic in their regulation of growth. The Igf2 gene encodes a paternally expressed ligand that promotes growth, while maternally expressed Igf2r encodes a cell surface receptor that restricts growth by sequestering Igf2 and targeting it for lysosomal degradation. There are now over 150 imprinted genes known in mammals, but no other clear examples of antagonistic gene pairs have been identified. The delta-like 1 gene (Dlk1) encodes a putative ligand that promotes fetal growth and in adults restricts adipose deposition. Conversely, Grb10 encodes an intracellular signalling adaptor protein that, when expressed from the maternal allele, acts to restrict fetal growth and is permissive for adipose deposition in adulthood. RESULTS: Here, using knockout mice, we present genetic and physiological evidence that these two factors exert their opposite effects on growth and physiology through a common signalling pathway. The major effects are on body size (particularly growth during early life), lean:adipose proportions, glucose regulated metabolism and lipid storage in the liver. A biochemical pathway linking the two cell signalling factors remains to be defined. CONCLUSIONS: We propose that Dlk1 and Grb10 define a mammalian growth axis that is separate from the IGF pathway, yet also features an antagonistic imprinted gene pair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-014-0099-8) contains supplementary material, which is available to authorized users

    Cache-Aware Query Processing with User Privacy Protection in Location-Based Services

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    Location-Based Service (LBS) providers can send geo-tagged data to mobile users who report their current location information. Location-related user privacy is a vital concern since untrusted LBS can monitor and misuse user location information. This paper aims at how to efficiently protect location privacy in query processing. In proxy-based location anonymizers, location cloaking algorithms need heavy bandwidth for query processing after blurring exact locations into a region. To alleviate it, the proposed query framework can integrate location cloaking and data caching. Next, we devise a novel location anonymization algorithm which takes advantage of the caching feature. Finally, we evaluate this solution experimentally for showing its improvement.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347619000023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Computer Science, Information SystemsComputer Science, Theory & MethodsEICPCI-S(ISTP)
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