144 research outputs found
FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function
Constructive pointfree topology eliminates non-constructive representation theorems from Riesz space theory
In Riesz space theory it is good practice to avoid representation theorems
which depend on the axiom of choice. Here we present a general methodology to
do this using pointfree topology. To illustrate the technique we show that
almost f-algebras are commutative. The proof is obtained relatively
straightforward from the proof by Buskes and van Rooij by using the pointfree
Stone-Yosida representation theorem by Coquand and Spitters
X-ray image reconstruction from a diffraction pattern alone
A solution to the inversion problem of scattering would offer aberration-free
diffraction-limited 3D images without the resolution and depth-of-field
limitations of lens-based tomographic systems. Powerful algorithms are
increasingly being used to act as lenses to form such images. Current image
reconstruction methods, however, require the knowledge of the shape of the
object and the low spatial frequencies unavoidably lost in experiments.
Diffractive imaging has thus previously been used to increase the resolution of
images obtained by other means. We demonstrate experimentally here a new
inversion method, which reconstructs the image of the object without the need
for any such prior knowledge.Comment: 5 pages, 3 figures, improved figures and captions, changed titl
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Lessons on Conditional Gene Targeting in Mouse Adipose Tissue
Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ∼2% of spermatozoa. Thus, different “adipocyte-specific” Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology
An algorithmic approach to the existence of ideal objects in commutative algebra
The existence of ideal objects, such as maximal ideals in nonzero rings,
plays a crucial role in commutative algebra. These are typically justified
using Zorn's lemma, and thus pose a challenge from a computational point of
view. Giving a constructive meaning to ideal objects is a problem which dates
back to Hilbert's program, and today is still a central theme in the area of
dynamical algebra, which focuses on the elimination of ideal objects via
syntactic methods. In this paper, we take an alternative approach based on
Kreisel's no counterexample interpretation and sequential algorithms. We first
give a computational interpretation to an abstract maximality principle in the
countable setting via an intuitive, state based algorithm. We then carry out a
concrete case study, in which we give an algorithmic account of the result that
in any commutative ring, the intersection of all prime ideals is contained in
its nilradical
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